US5284491A - Cardiac pacemaker with hysteresis behavior - Google Patents

Cardiac pacemaker with hysteresis behavior Download PDF

Info

Publication number
US5284491A
US5284491A US07/842,818 US84281892A US5284491A US 5284491 A US5284491 A US 5284491A US 84281892 A US84281892 A US 84281892A US 5284491 A US5284491 A US 5284491A
Authority
US
United States
Prior art keywords
rate
pacing
avg
interval
lrhi
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
US07/842,818
Inventor
Richard Sutton
Ivan Bourgeois
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Medtronic Inc
Original Assignee
Medtronic Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Medtronic Inc filed Critical Medtronic Inc
Priority to US07/842,818 priority Critical patent/US5284491A/en
Assigned to MEDTRONIC, INC. reassignment MEDTRONIC, INC. ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: BOURGEOIS, IVAN, SUTTON, RICHARD
Priority to PCT/US1993/000052 priority patent/WO1993016756A1/en
Priority to AU34331/93A priority patent/AU3433193A/en
Application granted granted Critical
Publication of US5284491A publication Critical patent/US5284491A/en
Priority to US08/547,350 priority patent/USRE37454E1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/362Heart stimulators
    • A61N1/365Heart stimulators controlled by a physiological parameter, e.g. heart potential

Definitions

  • the present invention relates to cardiac pacemakers, and more specifically to a pacemaker having a selectable hysteresis feature which compensates for sinus node malfunction.
  • Atrial or ventricular stimulations induced by such devices as cardiac pacemakers generally delay or inhibit natural heart activity by preventing the depolarization of the sinus node.
  • the hysteresis feature was developed to address this concern, by allowing the pacemaker to follow the sensed sinus node depolarization to a certain predetermined rate below the programmed lower rate of the pacemaker.
  • the escape interval in conventional demand pacemakers equipped with hysteresis feature is longer than the lower rate interval, for enabling the patient's intrinsic rhythm to control the heart as long as the intrinsic rate is maintained above a predetermined minimum rate.
  • these conventional pacemakers do not generally allow the natural heart activity to resume normally after pacing.
  • the Roline patent is incorporated herein by reference.
  • the above and further objects and features of the present invention are realized by providing a new and improved pacemaker having a hysteresis feature which permits intrinsic heart activity, controlled by the sinus node to resume optimally after pacing.
  • the pacemaker has a programmable lower rate and upper rate, a programmable lower hysteresis rate (LRH) corresponding to a lower rate hysteresis interval (LRHI), and a programmable rate (IR) intermediate an upper pacing rate (UR) and a lower pacing rate (LR).
  • a microprocessor measures the average rate of change in the intervals between consecutive ventricular depolarizations M AVG , and compares the last intrinsic escape (RR N ) interval to the lower rate hysteresis interval (LRHI).
  • the pacemaker stimulates at the lower rate hysteresis (LRH) and thereafter gradually increases the pacing rate up to the intermediate rate (IR) while the pulse generator is in the demand mode.
  • a time counter maintains a continuous pacing at the intermediate rate (IR) for a predefined period of time, and the pacing rate is gradually decreased down to the lower pacing rate (LR).
  • FIG. 1 is a block diagram showing the primary functional blocks of the pacemaker according to the present invention.
  • FIGS. 2A and 2B are flow charts of a simplified software program suitable for use in the pacemaker of FIG. 1;
  • FIG. 3 is an illustration of two exemplary generally increasing limit functions SL 1 and SL 2 which determine the behavior of the pacemaker according to the software program of FIGS. 2A and 2B;
  • FIG. 4 is a response curve illustrating the variation of the pacing rate according to the present invention.
  • FIG. 5 is another response curve illustrating pacing rate variation according to the present invention.
  • FIG. 6 is yet another response curve illustrating pacing rate variation according to the present invention.
  • Block 150 illustrates a microprocessor chip, such as the CDP 1802 microprocessor made by RCA.
  • the microprocessor 150 is connected to a ROM memory 151 and to a RAM memory 152 via a data bus 156.
  • An address bus 154 interconnects the ROM memory 151, the RAM memory 152, and a controller circuit 158.
  • the controller circuit 158 controls a pacer circuit 161 and a pacemaker output stage 160 for stimulating the heart.
  • the pacemaker 100 could be used for single chamber or dual chamber pacing.
  • FIGS. 2A and 2B together illustrate the flow diagram of a program 200 which is stored in the ROM memory 151, and which is run once each cycle in the pacemaker 100.
  • the program 200 could be stored in the RAM memory 152.
  • the program 200 does not contain all the steps which are carried out by the microprocessor 150, but it includes those steps that illustrate the operation of the pacemaker 100 according to the present invention. Several variables of the software-controlled operations can be reprogrammed through the RAM memory 152.
  • Intrinsic rhythm or “intrinsic rate” of the heart is the rate at which the heart naturally beats on its own, without being stimulated by a pacemaker-provided stimulus.
  • Hysteresis means extension of the range of rates at which inhibition of the pacemaker pulses will occur.
  • the base pacing interval is increased by the hysteresis interval.
  • hysteresis provides a longer escape interval, thereby giving the heart an opportunity to beat on its own before the pacer provides stimulation pulses.
  • Pacing Rate is the rate at which the stimulation pulses are provided from the heart from the pacemaker.
  • the program 200 is initiated, and the intrinsic ventricular depolarizations are sensed at 202. While the program 200 uses ventricular events for carrying out the invention, it should be understood that atrial events can alternatively be used.
  • the program 200 measures, at step 204, the intrinsic escape interval, such as the RR interval between two successive sensed ventricular events, and calculates, at step 206, a parameter "D", as follows:
  • RR i is the RR interval which has been recently measured at step 204; and RR i-1 is the RR interval preceding RR i . It therefore follows that the parameter D is indicative of the rate of change of the RR interval.
  • D the absolute value of D represents the rate of change of the intervals of the intrinsic ventricular depolarizations, which is also illustrated by the slope the curve AB in FIGS. 5 and 6, as it will be described later in greater detail.
  • step 208 If at step 208 the value of D is found to be negative, this value will not be used since it represents an increase in the intrinsic ventricular depolarization rate, and the above subroutine, including steps 202, 204, 206 and step 208, is repeated until a positive value of D is found.
  • the preferred embodiment of the present invention relates principally to precipitous drops in heart rates, and consequently only positive values of D are added and stored at 212 by the random access memory RAM 152.
  • the software 200 calculates the average rate of increase M AVG of a preselected number "N" of RR intervals.
  • M AVG is calculated over a predetermined period of time "T". If during that period T, the value of M AVG is less than a first limit function SL 1 , then this is an indication that the intrinsic heart rate has not dropped rapidly enough to warrant the use of corrective measures, such as the activation of the hysteresis feature. If on the other hand, the value of M AVG reaches or exceeds the first limit SL 1 , but is less than a second limit SL 2 , the pacemaker is instructed to take appropriate measures, as will be described later in greater detail.
  • the program 200 stores the calculated positive values of D, at step 212, and counts the number of events "n" indicative of a positive D value. When the count reaches a preprogrammed number "N" of stored beats or reaches the time period T, the program 200 calculates the sum "M" of the N stored values D, as follows: ##EQU1## where j is an integer that varies between 1 and N; and where N is the number of stored beats.
  • T 15 seconds. It should, however, be understood that different values or ranges of values can alternatively be employed within the scope of the invention.
  • LRI means the Lower Rate Interval which corresponds to the lower pacing rate "LR" of the pacemaker, where LRI in milliseconds equals 60,000 divided by LR in beats per minute. LR is typically programmed to 70 beats per minute.
  • LRHI means the Lower Rate Hysteresis Interval that corresponds to the lower rate hysteresis "LRH” which is typically programmed to 50 beats per minute. LRHI in milliseconds equals 60,000 divided by LRH in beats per minute.
  • SL 1 and SL 2 are boundaries between regions defining distinctly different operation of the pacemaker 100. For clarity purposes, the six regions are defined as follows:
  • Region I is the portion of the quadrant defined by the lower limit function SL 1 and by the RRI and time axes.
  • the pacemaker 100 operates in Region I whenever the value of M AVG is less than SL 1 ; and the last intrinsic ventricular escape interval RR N is shorter than the lower rate hysteresis interval LRHI. Pacing is inhibited in Region I, as illustrated by the curve KL in FIG. 4, and by step 222 of FIG. 2A.
  • the curve KL shows the heart rate decreasing at a slow rate.
  • Region II is the portion of the quadrant defined by the limit functions SL 1 and SL 2 , and by the lower rate hysteresis interval LRHI axis.
  • the pacemaker 100 operates in Region II whenever the value of M AVG is greater than SL 1 , but less than SL 2 ; and the last intrinsic ventricular escape interval RR N is shorter than LRHI. Pacing is inhibited in Region II, as illustrated by the curve AB in FIGS. 5 and 6, and by step 236 of FIG. 2B.
  • the curve AB shows the heart rate decreasing at an intermediate rate.
  • Region III is the portion of the quadrant defined by the upper limit function SL 2 , by the LRI axis and by the lower rate hysteresis interval LRHI axis.
  • the pacemaker 100 operates in Region III whenever the value of M AVG is greater than SL 2 ; and the last intrinsic escape interval RR N is shorter than LRHI. Pacing is inhibited in Region III, as illustrated by the curve K'L in FIG. 4, and by the step 232 of FIG. 2B.
  • the curve K'L shows the heart rate decreasing precipitously, as opposed to curve KL, which represents a more modest heart rate drop in Region I.
  • Region IV is the portion of the quadrant above the lower rate hysteresis interval LRHI axis, and defined by the RRI axis and by the upper limit function SL 2 .
  • the pacemaker 100 operates in Region IV whenever the value of M AVG is greater than SL 2 ; and the last intrinsic escape interval RR N will be longer than LRHI.
  • pacing is carried out at the lower rate LR. It should however be understood that pacing could be alternatively carried out at the lower rate hysteresis LRH.
  • Region V will be the portion of the quadrant above the lower rate hysteresis interval LRHI axis, between the two limit functions SL 1 and SL 2 .
  • the pacemaker 100 operates in Region V whenever the value of M AVG is less than SL 2 but greater than SL 1 , and the last intrinsic escape interval RR N is longer than LRHI.
  • pacing starts at the lower rate hysteresis rate LRH and gradually increases until the pacing rate reaches an intermediate pacing rate IR.
  • Pacing at IR is maintained for a predetermined period of time, and is thereafter gradually reduced until it reaches the lower rate LR. Pacing is maintained at the lower rate until the intrinsic rate exceeds the pacemaker lower rate, as illustrated by the curve FG in FIG. 5.
  • the pacemaker operation in Region V is triggered by an intermediate rate of decrease in the intrinsic hear rate.
  • Region VI is the portion of the quadrant defined by the lower limit function and by the lower limit function SL 1 .
  • the pacemaker 100 operates in Region VI whenever the value of M AVG is less than SL 1 ; and the last intrinsic ventricular escape interval RR N will be longer than the lower rate hysteresis interval LRHI.
  • pacing is carried out at the lower rate LR. It should however be understood that pacing could be alternatively carried out at the lower rate hysteresis LRH.
  • the program 200 compares M AVG to SL 1 and step 218. If M AVG is less than SL 1 , then a further determination is made at step 220 whether the last ventricular intrinsic escape interval RR N is less than or equal to LRHI. If it is, the pacemaker 100 operates in Region I, and pacing is inhibited, as indicated by step 222 in FIG. 2A and by the response curve KL in FIG. 4.
  • the pacemaker 100 will operate in Region IV, and stimulation is carried out at the lower pacing rate LR, as illustrated by the curve LPQ in FIG. 4.
  • the curves in FIGS. 4, 5 and 6 which are drawn in dashed lines indicate that pacing is inhibited, while the curves drawn in solid lines indicate that pacing is occurring.
  • step 226 determines whether M AVG is less than or equal to SL 2 . If M AVG is found to be greater than SL 2 then the pacemaker 100 will operate in either Region III or Region IV. A further decision is made at step 228 whether the last intrinsic escape interval RR N is less than or equal to the lower rate hysteresis interval (LRHI).
  • LRHI lower rate hysteresis interval
  • the pacemaker 100 will operate in Region III, and as indicated by step 232 of FIG. 2B, and by the curve K'L in FIG. 4, pacing will be inhibited. If on the other hand, it is determined at step 228, that RR N is greater than LRHI, then the pacemaker 100 will operate in Region IV and as indicated by step 230 of FIG. 2B, and by the curve LPQ in FIG. 4, pacing is carried out at the lower pacing rate (LR).
  • LR lower pacing rate
  • the pacemaker 100 identifies and reacts to intermediate drops in the intrinsic heart rate, whenever M AVG is found to be intermediate the limit functions SL 1 and SL 2 , as follows:
  • the pacemaker is caused to pace at a gradually increasing pacing rate until it reaches a predetermined intermediate pacing rate (IR) which is lower than, or in certain circumstances, equal to, the upper pacing rate (UR).
  • IR intermediate pacing rate
  • UR upper pacing rate
  • Demand pacing is maintained at the intermediate pacing rate (IR) for a predetermined period of time, and is thereafter reduced gradually.
  • the program 200 determines at step 234 whether the last intrinsic escape interval RR N is less than or equal to LRHI. If it is, then the pacemaker 100 will operate in Region II, and as indicated by step 236, and by the curve AB in FIGS. 5 and 6, pacing is inhibited.
  • step 234 If however, it is determined at step 234 that RR N will tend to be longer than LRHI, then the condition set forth in equation (6) above is satisfied, and the pacemaker 100 will operate in Region V, and will respond by pacing at the lower rate hysteresis (LRH) for a predetermined period of time or a preset number of beats, as illustrated by the dashed line BB' in FIG. 6, and by step 238 in FIG. 2B.
  • LLRH lower rate hysteresis
  • the pacemaker 100 could alternatively bypass step 238 and start pacing along curve BC (FIG. 5), with one paced beat at the lower rate hysteresis (LRH).
  • pacing is started at point B (FIG. 5) and the pacing rate is incrementally increased until it reaches the intermediate rate (IR).
  • the intermediate rate IR is programmable, and could be changed by the attending physician.
  • the incremental increase in the pacing rate is illustrated by the curves BC in FIGS. 5 and 6.
  • the pacemaker 100 is in the inhibited mode for single chamber pacemakers, or in the DDD or fully automated mode for dual chamber pacemakers.
  • the incremental increase of the pacing rate is achieved by steps 240 through 244, whereby the value of the pacing rate is incrementally increased by a center increment value X (step 240), and a determination is made at step 242 whether the pacing rate is less than or equal to IR. Once IR is reached, then, as indicated by step 244, a time counter is set to maintain the continuous pacing at that intermediate rate (IR) for a preselected programmable period of time, such as for five minutes. This continuous pacing at the intermediate rate is illustrated by curve CD in FIGS. 5 and 6. If during the execution of the subroutine 244 through 248, an intrinsic rhythm is sensed at 245, then the intrinsic rate prevails, and pacing is inhibited.
  • IR intermediate rate
  • the pacing rate is gradually decreased from the intermediate pacing rate (IR), toward the lower pacing rate (LR).
  • This decrement is achieved by the subroutine 250-252, where the pacing rate is decreased by a counter decrement value Y until the pacing rate reaches the lower rate LR.
  • the pacemaker 100 If decremental pacing is maintained until it reaches the lower rate LR, the pacemaker 100 starts pacing at that lower rate, as illustrated by the curve EF in FIG. 5, and the routine 200 is repeated. If an intrinsic rhythm is sensed at any time during the decremental change (curve DE') in the pacing rate, then the intrinsic rate prevails, and pacing is inhibited, as illustrated by the curve E'RS in FIG. 6. The subroutine 200 is thereafter repeated.
  • the new approach described in the present invention teaches away from the conventional hysteresis response feature.
  • the natural heart rate resumes and is tracked until it reaches the hysteresis rate. Thereafter, the pacing rate is increased until the intermediate rate (IR) is reached. Pacing at that intermediate rate is maintained for a predetermined period of time, and thereafter allowed to gradually decay toward the lower rate.
  • IR intermediate rate
  • the present invention can be made an integral part of single chamber and dual chamber pacemakers which operate in one or more of the programmed modes: SSI, SSIR, DDD, DDDR, DVI, DVIR, DDI and/or DDIR.
  • the present hysteresis feature can be applied to the atrial and/or ventricular channels of a dual chamber pacemaker.

Abstract

A pacemaker having a hysteresis feature which permits intrinsic heart activity, controlled by the sinus node to resume optimally after pacing. The pacemaker has a programmable lower rate and upper rate, a programmable lower hysteresis rate (LRH) corresponding to a lower rate hysteresis interval (LRHI), and a programmable rate (IR) intermediate an upper pacing rate (UR) and a lower pacing rate (LR). A microprocessor measures the average rate of change MAVG in the intervals between consecutive ventricular depolarizations, and compares the last intrinsic escape interval RRN to the lower rate hysteresis interval (LRHI).
If the last intrinsic escape interval RRN is longer than the lower rate hysteresis interval (LRHI), and if the value of MAVG is greater than a first preselected value SL1 but less than a second preselected value SL2, the pacemaker stimulates at the lower rate hysteresis (LRH) and thereafter gradually increases the pacing rate up to the intermediate rate (IR). A time counter maintains a continuous pacing at the intermediate rate (IR) for a predefined period of time, and the pacing rate is gradually decreased toward the lower pacing rate (LR).

Description

BACKGROUND OF THE INVENTION
The present invention relates to cardiac pacemakers, and more specifically to a pacemaker having a selectable hysteresis feature which compensates for sinus node malfunction.
It is well known that natural heart activity, including the depolarization of the sinus node provides optimum hemodynamic performance. Atrial or ventricular stimulations induced by such devices as cardiac pacemakers, generally delay or inhibit natural heart activity by preventing the depolarization of the sinus node.
The hysteresis feature was developed to address this concern, by allowing the pacemaker to follow the sensed sinus node depolarization to a certain predetermined rate below the programmed lower rate of the pacemaker. As such, the escape interval in conventional demand pacemakers equipped with hysteresis feature, is longer than the lower rate interval, for enabling the patient's intrinsic rhythm to control the heart as long as the intrinsic rate is maintained above a predetermined minimum rate. However, in selected patients, these conventional pacemakers do not generally allow the natural heart activity to resume normally after pacing.
The following patents provide a brief historical background for the development and use of the hysteresis feature as it relates to cardiac pacing technology. U.S. Pat. No. 4,856,523, entitled "RATE-RESPONSIVE PACEMAKER WITH AUTOMATIC MODE SWITCHING AND/OR VARIABLE HYSTERESIS RATE," issued to Sholder et al, on Aug. 15, 1989, describes the inclusion of the hysteresis feature in a rate-responsive pacemaker, in an attempt to prevent competition between the pacemaker and the heart's SA node, when the anterograde conduction path is restored. The Sholder patent proposes to vary the hysteresis rate as a function of the pacemaker sensor rate, to a predetermined level upon sensing of the natural heart contraction during the escape interval, as illustrated in FIG. 3B and 4.
U.S. Pat. No. 4,363,325 entitled "MODE ADAPTIVE PACER," issued to Roline et al, on Dec. 14, 1982, and assigned to Medtronic, Inc., discloses a multiple-mode pacer which automatically switches from an atrial synchronous mode to a ventricular inhibited mode when the intrinsic atrial rate drops below a preset hysteresis rate. The Roline patent is incorporated herein by reference.
While the above cited patents and other publications and studies relating to the hysteresis feature have attempted with varying degrees of success to allow the patient's intrinsic rhythm to control, none was completely successful in causing the natural heart activity to resume optimally after pacing.
SUMMARY OF THE INVENTION
Briefly, the above and further objects and features of the present invention are realized by providing a new and improved pacemaker having a hysteresis feature which permits intrinsic heart activity, controlled by the sinus node to resume optimally after pacing.
The pacemaker has a programmable lower rate and upper rate, a programmable lower hysteresis rate (LRH) corresponding to a lower rate hysteresis interval (LRHI), and a programmable rate (IR) intermediate an upper pacing rate (UR) and a lower pacing rate (LR). A microprocessor measures the average rate of change in the intervals between consecutive ventricular depolarizations MAVG, and compares the last intrinsic escape (RRN) interval to the lower rate hysteresis interval (LRHI).
If the last intrinsic ventricular interval(RRN) will be longer than the lower rate hysteresis interval (LRHI), and if the value of MAVG is greater than a first preselected value SL1 but less than a second preselected value SL2, the pacemaker stimulates at the lower rate hysteresis (LRH) and thereafter gradually increases the pacing rate up to the intermediate rate (IR) while the pulse generator is in the demand mode. A time counter maintains a continuous pacing at the intermediate rate (IR) for a predefined period of time, and the pacing rate is gradually decreased down to the lower pacing rate (LR).
The accompanying Table I summarizes the features offered by the present invention, and correlates these features to FIGS. 2A through 6.
              TABLE I                                                     
______________________________________                                    
FIG. 2A                                                                   
       FIG. 2B  FIG. 3   FIG. 4 FIG. 5 FIG. 6                             
(Step) (Step)   (Region) (Curve)                                          
                                (Curve)                                   
                                       (Curve)                            
______________________________________                                    
220,            I        KL                                               
222                                                                       
220,            VI       LPQ                                              
224                                                                       
       226,     III       K'L                                               
       228,                                                               
       232                                                                
       226,      IV       LPQ                                               
       228,                                                               
       230                                                                
       226,     II              AB     AB                                 
       234,                                                               
       236                                                                
       226,     V               BCDEF  BB'CDE'R                           
       234,                                                               
       238-254                                                            
______________________________________                                    
BRIEF DESCRIPTION OF THE DRAWINGS
The above and other options, features and advantages of the present invention will be more apparent from the following more particular description thereof, presented in conjunction with accompanying drawings, wherein:
FIG. 1 is a block diagram showing the primary functional blocks of the pacemaker according to the present invention;
FIGS. 2A and 2B are flow charts of a simplified software program suitable for use in the pacemaker of FIG. 1;
FIG. 3 is an illustration of two exemplary generally increasing limit functions SL1 and SL2 which determine the behavior of the pacemaker according to the software program of FIGS. 2A and 2B;
FIG. 4 is a response curve illustrating the variation of the pacing rate according to the present invention;
FIG. 5 is another response curve illustrating pacing rate variation according to the present invention; and
FIG. 6 is yet another response curve illustrating pacing rate variation according to the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings and more particularly to FIG. 1 thereof, there is illustrated a block diagram of the components of the pacemaker 100 of the present invention. Block 150 illustrates a microprocessor chip, such as the CDP 1802 microprocessor made by RCA. The microprocessor 150 is connected to a ROM memory 151 and to a RAM memory 152 via a data bus 156. An address bus 154 interconnects the ROM memory 151, the RAM memory 152, and a controller circuit 158. The controller circuit 158, in turn, controls a pacer circuit 161 and a pacemaker output stage 160 for stimulating the heart. The pacemaker 100 could be used for single chamber or dual chamber pacing.
FIGS. 2A and 2B together illustrate the flow diagram of a program 200 which is stored in the ROM memory 151, and which is run once each cycle in the pacemaker 100. Alternatively, the program 200 could be stored in the RAM memory 152. The program 200 does not contain all the steps which are carried out by the microprocessor 150, but it includes those steps that illustrate the operation of the pacemaker 100 according to the present invention. Several variables of the software-controlled operations can be reprogrammed through the RAM memory 152.
Before proceeding with a more detailed explanation of the present invention, it would be helpful to review the following definitions:
"Intrinsic rhythm" or "intrinsic rate" of the heart is the rate at which the heart naturally beats on its own, without being stimulated by a pacemaker-provided stimulus.
"Hysteresis" means extension of the range of rates at which inhibition of the pacemaker pulses will occur. The base pacing interval is increased by the hysteresis interval. Thus, hysteresis provides a longer escape interval, thereby giving the heart an opportunity to beat on its own before the pacer provides stimulation pulses.
"Pacing Rate" is the rate at which the stimulation pulses are provided from the heart from the pacemaker.
Starting at step 201, the program 200 is initiated, and the intrinsic ventricular depolarizations are sensed at 202. While the program 200 uses ventricular events for carrying out the invention, it should be understood that atrial events can alternatively be used.
The program 200 measures, at step 204, the intrinsic escape interval, such as the RR interval between two successive sensed ventricular events, and calculates, at step 206, a parameter "D", as follows:
D=RR.sub.i -RR.sub.i-1,                                    (1)
where RRi is the RR interval which has been recently measured at step 204; and RRi-1 is the RR interval preceding RRi. It therefore follows that the parameter D is indicative of the rate of change of the RR interval.
In this respect, if D were found to have a positive value, it is an indication that the RR interval is increasing with time, and consequently the intrinsic rate of the heart is dropping. The reverse holds true where D has a negative value, indicating that the RR interval is decreasing and that the intrinsic rate is increasing. Additionally, the absolute value of D represents the rate of change of the intervals of the intrinsic ventricular depolarizations, which is also illustrated by the slope the curve AB in FIGS. 5 and 6, as it will be described later in greater detail.
If at step 208 the value of D is found to be negative, this value will not be used since it represents an increase in the intrinsic ventricular depolarization rate, and the above subroutine, including steps 202, 204, 206 and step 208, is repeated until a positive value of D is found. The dashed line 207 indicates that if the value of D is found to be negative, then the attending physician will have the option to either cause the software to set n=0, at step 203, or to restart at step 202. The preferred embodiment of the present invention relates principally to precipitous drops in heart rates, and consequently only positive values of D are added and stored at 212 by the random access memory RAM 152.
While the preferred embodiment includes adding only those positive values of D, it will become apparent to those skilled in the art that consecutive D values could alternatively be added. The feature of selecting between consecutive and positive D values is a programmable feature, and is selectable by the attending physician.
In order to detect and ascertain the occurrence of precipitous heart rate drops, the software 200 calculates the average rate of increase MAVG of a preselected number "N" of RR intervals. Preferably, MAVG is calculated over a predetermined period of time "T". If during that period T, the value of MAVG is less than a first limit function SL1, then this is an indication that the intrinsic heart rate has not dropped rapidly enough to warrant the use of corrective measures, such as the activation of the hysteresis feature. If on the other hand, the value of MAVG reaches or exceeds the first limit SL1, but is less than a second limit SL2, the pacemaker is instructed to take appropriate measures, as will be described later in greater detail.
To achieve this function, the program 200 stores the calculated positive values of D, at step 212, and counts the number of events "n" indicative of a positive D value. When the count reaches a preprogrammed number "N" of stored beats or reaches the time period T, the program 200 calculates the sum "M" of the N stored values D, as follows: ##EQU1## where j is an integer that varies between 1 and N; and where N is the number of stored beats.
The value of M is then averaged at step 217 over the number of stored beats N, as follows: ##EQU2##
In the preferred mode of the present invention the above parameters are assigned the following values:
N=6 beats.
T=15 seconds. It should, however, be understood that different values or ranges of values can alternatively be employed within the scope of the invention.
Digressing from the flow chart of FIG. 2A, and turning to FIG. 3, there is a shown lower limit function SL1 and an upper limit function SL2 which are identified by the numeral references 10 and 12, and which divide the quadrant into six regions: I, II, III, IV, V and VI. Each one of these regions will now be described in greater detail in relation to FIGS. 2A through 5. The horizontal coordinate axis represents time "t", and the vertical coordinate axis represents RR intervals "RRI".
As used in this specification, the LRI and LRHI parameters in the following context:
"LRI" means the Lower Rate Interval which corresponds to the lower pacing rate "LR" of the pacemaker, where LRI in milliseconds equals 60,000 divided by LR in beats per minute. LR is typically programmed to 70 beats per minute.
"LRHI" means the Lower Rate Hysteresis Interval that corresponds to the lower rate hysteresis "LRH" which is typically programmed to 50 beats per minute. LRHI in milliseconds equals 60,000 divided by LRH in beats per minute.
By comparing the average rate of change MAVG to the programmable limit functions SL1 and SL2, it would be possible to identify the region which corresponds to the mode of operation of the pacemaker 100. SL1 and SL2 are boundaries between regions defining distinctly different operation of the pacemaker 100. For clarity purposes, the six regions are defined as follows:
"Region I" is the portion of the quadrant defined by the lower limit function SL1 and by the RRI and time axes. The pacemaker 100 operates in Region I whenever the value of MAVG is less than SL1 ; and the last intrinsic ventricular escape interval RRN is shorter than the lower rate hysteresis interval LRHI. Pacing is inhibited in Region I, as illustrated by the curve KL in FIG. 4, and by step 222 of FIG. 2A. The curve KL shows the heart rate decreasing at a slow rate.
"Region II" is the portion of the quadrant defined by the limit functions SL1 and SL2, and by the lower rate hysteresis interval LRHI axis. The pacemaker 100 operates in Region II whenever the value of MAVG is greater than SL1, but less than SL2 ; and the last intrinsic ventricular escape interval RRN is shorter than LRHI. Pacing is inhibited in Region II, as illustrated by the curve AB in FIGS. 5 and 6, and by step 236 of FIG. 2B. The curve AB shows the heart rate decreasing at an intermediate rate.
"Region III" is the portion of the quadrant defined by the upper limit function SL2, by the LRI axis and by the lower rate hysteresis interval LRHI axis. The pacemaker 100 operates in Region III whenever the value of MAVG is greater than SL2 ; and the last intrinsic escape interval RRN is shorter than LRHI. Pacing is inhibited in Region III, as illustrated by the curve K'L in FIG. 4, and by the step 232 of FIG. 2B. The curve K'L shows the heart rate decreasing precipitously, as opposed to curve KL, which represents a more modest heart rate drop in Region I.
"Region IV" is the portion of the quadrant above the lower rate hysteresis interval LRHI axis, and defined by the RRI axis and by the upper limit function SL2. The pacemaker 100 operates in Region IV whenever the value of MAVG is greater than SL2 ; and the last intrinsic escape interval RRN will be longer than LRHI. As illustrated by the curve LPQ in FIG. 4, and by the step 230 of FIG. 2B, pacing is carried out at the lower rate LR. It should however be understood that pacing could be alternatively carried out at the lower rate hysteresis LRH.
"Region V" will be the portion of the quadrant above the lower rate hysteresis interval LRHI axis, between the two limit functions SL1 and SL2. The pacemaker 100 operates in Region V whenever the value of MAVG is less than SL2 but greater than SL1, and the last intrinsic escape interval RRN is longer than LRHI. As illustrated by the curves BCDEF and BB'CDE'R in FIGS. 5 and 6 respectively, and by steps 238 through 254 of FIG. 2B, pacing starts at the lower rate hysteresis rate LRH and gradually increases until the pacing rate reaches an intermediate pacing rate IR. Pacing at IR is maintained for a predetermined period of time, and is thereafter gradually reduced until it reaches the lower rate LR. Pacing is maintained at the lower rate until the intrinsic rate exceeds the pacemaker lower rate, as illustrated by the curve FG in FIG. 5. The pacemaker operation in Region V is triggered by an intermediate rate of decrease in the intrinsic hear rate.
"Region VI" is the portion of the quadrant defined by the lower limit function and by the lower limit function SL1. The pacemaker 100 operates in Region VI whenever the value of MAVG is less than SL1 ; and the last intrinsic ventricular escape interval RRN will be longer than the lower rate hysteresis interval LRHI. As illustrated by the curve LPQ in FIG. 4, and by the step 224 of FIG. 2A, pacing is carried out at the lower rate LR. It should however be understood that pacing could be alternatively carried out at the lower rate hysteresis LRH.
Returning now to FIG. 2A, the program 200 compares MAVG to SL1 and step 218. If MAVG is less than SL1, then a further determination is made at step 220 whether the last ventricular intrinsic escape interval RRN is less than or equal to LRHI. If it is, the pacemaker 100 operates in Region I, and pacing is inhibited, as indicated by step 222 in FIG. 2A and by the response curve KL in FIG. 4.
If the intrinsic escape interval (RRN) is determined at step 220, to be equal to or tend to exceed LRHI, and if there is no sensed event at a shorter interval, while the pacemaker is still in the demand mode, the pacemaker 100 will operate in Region IV, and stimulation is carried out at the lower pacing rate LR, as illustrated by the curve LPQ in FIG. 4. The curves in FIGS. 4, 5 and 6 which are drawn in dashed lines indicate that pacing is inhibited, while the curves drawn in solid lines indicate that pacing is occurring.
Returning now to step 218 in the flow chart of FIG. 2A, if the program 200 determines that MAVG is greater than or equal to SL1 then a further determination is made at step 226 whether MAVG is less than or equal to SL2. If MAVG is found to be greater than SL2 then the pacemaker 100 will operate in either Region III or Region IV. A further decision is made at step 228 whether the last intrinsic escape interval RRN is less than or equal to the lower rate hysteresis interval (LRHI).
If the program 200 determines that RRN is less than or equal to LRHI then the pacemaker 100 will operate in Region III, and as indicated by step 232 of FIG. 2B, and by the curve K'L in FIG. 4, pacing will be inhibited. If on the other hand, it is determined at step 228, that RRN is greater than LRHI, then the pacemaker 100 will operate in Region IV and as indicated by step 230 of FIG. 2B, and by the curve LPQ in FIG. 4, pacing is carried out at the lower pacing rate (LR).
The pacemaker 100 identifies and reacts to intermediate drops in the intrinsic heart rate, whenever MAVG is found to be intermediate the limit functions SL1 and SL2, as follows:
SL.sub.1 ≦M.sub.AVG ≦SL.sub.2                (4)
In the above condition, the pacemaker is caused to pace at a gradually increasing pacing rate until it reaches a predetermined intermediate pacing rate (IR) which is lower than, or in certain circumstances, equal to, the upper pacing rate (UR). Demand pacing is maintained at the intermediate pacing rate (IR) for a predetermined period of time, and is thereafter reduced gradually.
With reference to FIG. 2B, the program 200 determines at step 234 whether the last intrinsic escape interval RRN is less than or equal to LRHI. If it is, then the pacemaker 100 will operate in Region II, and as indicated by step 236, and by the curve AB in FIGS. 5 and 6, pacing is inhibited.
If however, it is determined at step 234 that RRN will tend to be longer than LRHI, then the condition set forth in equation (6) above is satisfied, and the pacemaker 100 will operate in Region V, and will respond by pacing at the lower rate hysteresis (LRH) for a predetermined period of time or a preset number of beats, as illustrated by the dashed line BB' in FIG. 6, and by step 238 in FIG. 2B.
It should however be understood that the pacemaker 100 could alternatively bypass step 238 and start pacing along curve BC (FIG. 5), with one paced beat at the lower rate hysteresis (LRH). In this respect, pacing is started at point B (FIG. 5) and the pacing rate is incrementally increased until it reaches the intermediate rate (IR). The intermediate rate IR is programmable, and could be changed by the attending physician. The incremental increase in the pacing rate is illustrated by the curves BC in FIGS. 5 and 6. During this period, the pacemaker 100 is in the inhibited mode for single chamber pacemakers, or in the DDD or fully automated mode for dual chamber pacemakers.
The incremental increase of the pacing rate is achieved by steps 240 through 244, whereby the value of the pacing rate is incrementally increased by a center increment value X (step 240), and a determination is made at step 242 whether the pacing rate is less than or equal to IR. Once IR is reached, then, as indicated by step 244, a time counter is set to maintain the continuous pacing at that intermediate rate (IR) for a preselected programmable period of time, such as for five minutes. This continuous pacing at the intermediate rate is illustrated by curve CD in FIGS. 5 and 6. If during the execution of the subroutine 244 through 248, an intrinsic rhythm is sensed at 245, then the intrinsic rate prevails, and pacing is inhibited.
Once the counter time lapses, then, as illustrated by the curves DE and DE' in FIG. 5 and 6 respectively, the pacing rate is gradually decreased from the intermediate pacing rate (IR), toward the lower pacing rate (LR). This decrement is achieved by the subroutine 250-252, where the pacing rate is decreased by a counter decrement value Y until the pacing rate reaches the lower rate LR.
If decremental pacing is maintained until it reaches the lower rate LR, the pacemaker 100 starts pacing at that lower rate, as illustrated by the curve EF in FIG. 5, and the routine 200 is repeated. If an intrinsic rhythm is sensed at any time during the decremental change (curve DE') in the pacing rate, then the intrinsic rate prevails, and pacing is inhibited, as illustrated by the curve E'RS in FIG. 6. The subroutine 200 is thereafter repeated.
It is therefore clear that the new approach described in the present invention teaches away from the conventional hysteresis response feature. In the present invention, whenever an intermediate drop in the heart rate occurs and the hysteresis feature is activated, the natural heart rate resumes and is tracked until it reaches the hysteresis rate. Thereafter, the pacing rate is increased until the intermediate rate (IR) is reached. Pacing at that intermediate rate is maintained for a predetermined period of time, and thereafter allowed to gradually decay toward the lower rate.
It should become apparent to those skilled in the art after reviewing the present description, that the present invention can be made an integral part of single chamber and dual chamber pacemakers which operate in one or more of the programmed modes: SSI, SSIR, DDD, DDDR, DVI, DVIR, DDI and/or DDIR. The present hysteresis feature can be applied to the atrial and/or ventricular channels of a dual chamber pacemaker.
While the following ranges reflect exemplary values of IR, LR, UR, LRH, SL1 and SL2, it should be understood to those skilled in the art that other values and ranges can also be employed and/or programmed.
100 bpm≦UR≦150 bpm.
80 bpm≦IR≦100 bpm.
60 bpm≦LR≦80 bpm.
40 bpm≦LRH≦60 bpm.
2%≦SL.sub.1 ≦10%.
5%≦SL.sub.2 ≦20%.
4 beats≦N≦16 beats.
While particular embodiments of the present invention have been disclosed, it is to be understood that various different modifications are possible and are contemplated within the scope and spirit of the specification, drawings, abstract, and appended claims.

Claims (22)

What is claimed is:
1. In a pacemaker having a programmable lower rate and upper rate, a programmable lower rate hysteresis (LRH) corresponding to a lower rate hysteresis interval (LRHI), and a programmable intermediate pacing rate (IR) the improvement comprising:
A. means for measuring rate of change MAVG of successive cardiac intrinsic escape intervals;
B. means for comparing MAVG to a first predefined limit SL1 ;
C. means for comparing the last intrinsic escape interval to the lower rate hysteresis interval (LRHI); and
D. means for stimulating a heart at the lower rate hysteresis (LRH) and for gradually incrementing a pacing rate until the pacing ratio reaches the intermediate pacing rate (IR) if the last intrinsic escape interval is longer than the lower rate hysteresis interval (LRHI) and if said MAVG is greater than SL1.
2. The pacemaker according to claim 1 further comprising:
A. time counter means for maintaining continuous pacing at the intermediate rate (IR) for a predefined period of time; and
B. means for allowing gradual decay of the pacing rate after said selected period of time has lapsed.
3. The pacemaker according to claim 2, wherein said selected programmable time is set equal to five minutes.
4. The pacemaker according to claim 1, wherein said means for measuring the rate of change MAVG comprising:
A. means for measuring intervals between two successive ventricular depolarizations (RR intervals); and
B. means for averaging the rate of change MAVG of said successive RR intervals.
5. The pacemaker according to claim 4, wherein said means for averaging the rate of change of said RR intervals comprises:
A. means for calculating a difference D between two successive RR intervals;
B. means for comparing said difference D to a predetermined reference value;
C. means for storing those values of D which are greater than said reference value;
D. means for calculating a sum M of N stored values of D, wherein N is a predetermined positive integer; and
E. means for setting MAVG equal to M/N.
6. The pacemaker according to claim 5, wherein said means for averaging MAVG comprising means for averaging the values of D greater than said reference value over a predefined period of time.
7. The pacemaker according to claim 6, wherein said reference value is zero, and wherein only positive values of D are stored and added.
8. The pacemaker according to claim 5, wherein N is set equal to six beats.
9. The pacemaker according to claim 4, further including means for comparing MAVG to a second predetermined limit SL2 wherein SL2 has a value greater than that of SL1.
10. The pacemaker according to claim 9, wherein said means for stimulating gradually increments the pacing rate until the pacing rate reaches the intermediate pacing rate (IR), if the last intrinsic escape interval RRN is longer than LRHI, and if MAVG is greater than or equal to SL1 but less than or equal to SL2.
11. The pacemaker according to claim 9, further comprising means for inhibiting stimulation if MAVG is greater than SL2, and if the RRN interval is less than or equal to LRHI.
12. The pacemaker according to claim 11, further comprising means for stimulating at the lower rate if MAVG is greater than SL2, and if the RRN interval will be longer than LRHI.
13. The pacemaker according to claim 11, further comprising:
A. means for inhibiting stimulation if MAVG is greater than SL2, and if the RRN interval is less than or equal to LRH; and
B. means for stimulating at the lower rate if MAVG is greater than SL2, and if the RRN interval will be longer than LRHI.
14. The pacemaker according to claim 4, further including means for inhibiting stimulation if MAVG is less than SL1, and if the last intrinsic escape interval RRN is less than or equal to LRHI.
15. The pacemaker according to claim 14, further comprising means for stimulating at the lower rate if MAVG is less than SL1, and if the RRN interval will be greater than LRHI.
16. A method for pacing with a pacemaker having a programmable lower rate and upper rate, a programmable lower hysteresis rate (LRH) corresponding to a lower rate hysteresis interval (LRHI), and a programmable intermediate pacing rate (IR), the pacing method comprising the steps of:
A. measuring a rate of change of MAVG of successive intrinsic escape intervals;
B. comparing MAVG to a first predetermined limit SL1 ;
C. comparing a last intrinsic escape interval RRN to the lower rate hysteresis interval (LRHI); and
D. stimulating at the lower rate hysteresis (LRH) and gradually incrementing a pacing rate until it reaches the intermediate pacing rate (IR) if the RRN interval will be longer than the lower rate hysteresis interval (LRHI) and if said MAVG is greater than SL1.
17. The pacing method according to claim 16 further comprising the steps of:
A. maintaining continuous pacing at the intermediate rate (IR) for a predefined period of time; and
B. allowing gradual decay of the pacing rate after said selected period of time has lapsed.
18. The pacing method according to claim 17, wherein, said step of measuring the rate of change MAVG comprises:
A. measuring intervals between two successive ventricular depolarizations (RR intervals); and
B. averaging the rate of change MAVG of said successive RR intervals;
19. The pacing method according to claim 18, wherein said step of averaging the rate of change of said RR intervals comprises:
A. calculating a difference D between two successive RR intervals;
B. comparing the difference D to a predetermined reference value;
C. storing those values of D which are greater than said reference value;
D. calculating a sum M of N stored values of D, wherein N is a predetermined positive integer; and
E. setting MAVG equal to M/N.
20. The pacing method according to claim 19, further comprising the step comparing MAVG to a second predetermined limit SL2, wherein SL2 has a value greater than that of SL1.
21. The pacing method according to claim 20, wherein said step of stimulating comprises gradually incrementing the pacing rate until it reaches the intermediate pacing rate (IR), if the RRN interval will be longer than LRHI, and if MAVG is greater than or equal to SL1 but less than or equal to SL2.
22. The pacing method according to claim 18, further comprises:
A. the step of inhibiting stimulation if MAVG is less than SL1, and if the last sensed RR interval is less than or equal to LRHI;
B. the step of stimulating at the lower rate if MAVG is less than SL1, and if the RRN interval will be longer than LRHI;
C. the step of inhibiting stimulation if MAVG is greater than SL2, and if the RRN interval is less than or equal to LRHI; and
D. the step of stimulating at the lower rate if MAVG is greater than SL2, and if the RRN interval will be longer than LRHI.
US07/842,818 1992-02-27 1992-02-27 Cardiac pacemaker with hysteresis behavior Ceased US5284491A (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US07/842,818 US5284491A (en) 1992-02-27 1992-02-27 Cardiac pacemaker with hysteresis behavior
PCT/US1993/000052 WO1993016756A1 (en) 1992-02-27 1993-01-04 Cardiac pacemaker with hysteresis behavior
AU34331/93A AU3433193A (en) 1992-02-27 1993-01-04 Cardiac pacemaker with hysteresis behavior
US08/547,350 USRE37454E1 (en) 1992-02-27 1995-10-24 Cardiac pacemaker with hystersis behavior

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US07/842,818 US5284491A (en) 1992-02-27 1992-02-27 Cardiac pacemaker with hysteresis behavior

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US08/547,350 Reissue USRE37454E1 (en) 1992-02-27 1995-10-24 Cardiac pacemaker with hystersis behavior

Publications (1)

Publication Number Publication Date
US5284491A true US5284491A (en) 1994-02-08

Family

ID=25288311

Family Applications (2)

Application Number Title Priority Date Filing Date
US07/842,818 Ceased US5284491A (en) 1992-02-27 1992-02-27 Cardiac pacemaker with hysteresis behavior
US08/547,350 Expired - Lifetime USRE37454E1 (en) 1992-02-27 1995-10-24 Cardiac pacemaker with hystersis behavior

Family Applications After (1)

Application Number Title Priority Date Filing Date
US08/547,350 Expired - Lifetime USRE37454E1 (en) 1992-02-27 1995-10-24 Cardiac pacemaker with hystersis behavior

Country Status (3)

Country Link
US (2) US5284491A (en)
AU (1) AU3433193A (en)
WO (1) WO1993016756A1 (en)

Cited By (117)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5501701A (en) * 1994-04-29 1996-03-26 Medtronic, Inc. Pacemaker with vasovagal syncope detection and therapy
US5540728A (en) * 1994-05-20 1996-07-30 Medtronic, Inc. Pacemaker with vasovagal snycope detection
WO1997011745A1 (en) * 1995-09-29 1997-04-03 Medtronic, Inc. Modification of pacemaker tachy response based on ffrw sensing
US5676686A (en) * 1994-05-20 1997-10-14 Medtronic, Inc. Pacemaker with vasovagal syncope detection
WO1997045161A1 (en) * 1996-05-28 1997-12-04 Biotronik Mess-und Therapiegeräte GmbH & Co. Ingenieurbüro Berlin Demand pacemaker with hysteresis function
US5706829A (en) * 1996-06-06 1998-01-13 Creighton University Method for treating neurocardiogenic syncope
US5713929A (en) * 1996-05-03 1998-02-03 Medtronic, Inc. Arrhythmia and fibrillation prevention pacemaker using ratchet up and decay modes of operation
US5725561A (en) * 1995-06-09 1998-03-10 Medtronic, Inc. Method and apparatus for variable rate cardiac stimulation
US5782886A (en) * 1997-02-28 1998-07-21 Vitatron Medical, B.V. Pacemaker with improved hysteresis
US5814083A (en) * 1995-09-29 1998-09-29 Medtronic, Inc Pacemaker tachy determination based blocked on 2:1 sensing
FR2763247A1 (en) * 1997-05-16 1998-11-20 Ela Medical Sa ACTIVE IMPLANTABLE MEDICAL DEVICE, IN PARTICULAR A CARDIAC STIMULATOR, DEFIBRILLATOR AND / OR CARDIOVERTER FOR REDUCING ARRHYTHMIA EPISODES, ESPECIALLY ATRIAL ARRHYTHMIA
US5991659A (en) * 1998-09-30 1999-11-23 Vitatron Medical, B.V. Pacing system with full range sudden rate drop detection and responsive pacing intervention
US6049735A (en) * 1999-03-01 2000-04-11 Cardiac Pacemakers Inc. Cardiac rhythm management device with detection and therapy for sudden syncopal events
WO2000027475A1 (en) * 1998-11-06 2000-05-18 Impulse Dynamics Nv Sensor-based regulation of excitable tissue control of the heart
US6285907B1 (en) 1999-05-21 2001-09-04 Cardiac Pacemakers, Inc. System providing ventricular pacing and biventricular coordination
US6351669B1 (en) 1999-05-21 2002-02-26 Cardiac Pacemakers, Inc. Cardiac rhythm management system promoting atrial pacing
US20020052632A1 (en) * 1996-01-08 2002-05-02 Shlomo Ben-Haim Electrical muscle controller
WO2002045792A2 (en) 2000-12-04 2002-06-13 Medtronic, Inc. Method and system for preventing the recurrence of atrial fibrillation by an implantable medical device
US20020082660A1 (en) * 2000-12-26 2002-06-27 Stahmann Jeffrey E Apparatus and method for pacing mode switching during atrial tachyarrhythmias
US20020082509A1 (en) * 2000-12-26 2002-06-27 Scott Vanderlinde Method and system for display of cardiac event intervals in a resynchronization pacemaker
US20020091415A1 (en) * 2000-05-13 2002-07-11 Lovett Eric G. Rate smoothing control
US6430438B1 (en) 1999-05-21 2002-08-06 Cardiac Pacemakers, Inc. Cardiac rhythm management system with atrial shock timing optimization
US6501988B2 (en) 2000-12-26 2002-12-31 Cardiac Pacemakers Inc. Apparatus and method for ventricular rate regularization with biventricular sensing
US6522922B1 (en) 2000-07-13 2003-02-18 Cardiac Pacemakers, Inc. Method and apparatus for breaking pacemaker mediated bradycardia
US20030040777A1 (en) * 1996-01-08 2003-02-27 Itzik Shemer Modulation of intracellular calcium concentration using non-excitatory electrical signals applied to the tissue
US20030055464A1 (en) * 1999-03-05 2003-03-20 Nissim Darvish Blood glucose level control
US20030078630A1 (en) * 2000-05-26 2003-04-24 Cardiac Pacemakers, Inc. Rate smoothing control
US6587721B1 (en) 1998-11-06 2003-07-01 Impulse Dynamics N.V. Trigger-based regulation of excitable tissue control of the heart
WO2003061759A1 (en) 2002-01-22 2003-07-31 Medtronic, Inc. Methods and apparatus for detection and treatment of syncope
US6625492B2 (en) 2000-05-15 2003-09-23 Pacesetter, Inc. Implantable cardiac stimulation device with detection and therapy for patients with vasovagal syncope
US6647295B2 (en) 2000-05-15 2003-11-11 Pacesetter, Inc. Implantable cardiac stimulation device with detection and therapy for patients with vasovagal syncope
US20030233131A1 (en) * 1999-05-21 2003-12-18 Kramer Andrew P. Apparatus and method for ventricular rate regularization
EP1374947A2 (en) 1994-04-29 2004-01-02 Medtronic, Inc. Pacemaker with vasovagal syncope detection
US6675043B1 (en) 1998-11-06 2004-01-06 Impulse Dynamics N.V. Sensor-based regulation of excitable tissue control of the heart
US20040010295A1 (en) * 2000-12-29 2004-01-15 Cardiac Pacemakers, Inc. Apparatus and method for ventricular rate regularization
US6687541B2 (en) 2000-09-14 2004-02-03 Cardiac Pacemakers, Inc. Method for delivering atrial defibrillation therapy
US20040073093A1 (en) * 2002-10-11 2004-04-15 Cardiac Pacemakers, Inc. Methods and devices for detection of context when addressing a medical condition of a patient
US6725093B1 (en) 1998-11-06 2004-04-20 Impulse Dynamics N.V. Regulation of excitable tissue control of the heart based on physiological input
US6763267B2 (en) 2000-07-13 2004-07-13 Cardiac Pacemakers, Inc. Ventricular conduction delay trending system and method
US20040172076A1 (en) * 1999-05-21 2004-09-02 Stahmann Jeffrey E. Apparatus and method for pacing mode switching during atrial tachyarrhythmias
US20040210260A1 (en) * 2003-04-16 2004-10-21 Medtronic, Inc. Pacemaker with vasovagal syncope detection and therapy
US20040215259A1 (en) * 1999-05-21 2004-10-28 Cardiac Pacemakers, Inc. Method and apparatus for treating irregular ventricular contractions such as during atrial arrhythmia
US20040243190A1 (en) * 1996-01-08 2004-12-02 Shlomo Ben-Haim Electrical muscle controller
US6829504B1 (en) 2000-09-14 2004-12-07 Cardiac Pacemakers, Inc. System and method for preventing recurrence of atrial tachyarrhythmia
US20040249421A1 (en) * 2000-09-13 2004-12-09 Impulse Dynamics Nv Blood glucose level control
US20050080347A1 (en) * 2003-10-10 2005-04-14 Medtronic, Inc. Method and apparatus for detecting and discriminating arrhythmias
US6889078B2 (en) 2001-04-26 2005-05-03 Medtronic, Inc. Hysteresis activation of accelerated pacing
US20050137633A1 (en) * 2003-12-22 2005-06-23 Salo Rodney W. Pacing method and device for preserving native conduction system
US20050180958A1 (en) * 1999-02-04 2005-08-18 Technion Research & Development Foundation Ltd. Method and apparatus for maintenance and expansion of hemopoietic stem cells and/or progenitor cells
US7027863B1 (en) 1999-10-25 2006-04-11 Impulse Dynamics N.V. Device for cardiac therapy
US20060085045A1 (en) * 1999-03-05 2006-04-20 Metacure N.V. Blood glucose level control
US7039461B1 (en) 2000-05-13 2006-05-02 Cardiac Pacemakers, Inc. Cardiac pacing system for prevention of ventricular fibrillation and ventricular tachycardia episode
US20060184207A1 (en) * 1999-03-05 2006-08-17 Metacure N.V. Blood glucose level control
US20060212079A1 (en) * 1999-10-25 2006-09-21 Routh Andre G Cardiac contractility modulation device having anti-arrhythmic capabilities and method of operating thereof
US20070016258A1 (en) * 1999-05-21 2007-01-18 Cardiac Pacemakers, Inc. Method and apparatus for treating irregular ventricular contractions such as during atrial arrhythmia
US20070027493A1 (en) * 2003-07-21 2007-02-01 Shlomo Ben-Haim Gastrointestinal methods and apparatus for use in treating disorders and controlling blood sugar
US20070027487A1 (en) * 2003-03-10 2007-02-01 Impulse Dynamics Nv Apparatus and method for delivering electrical signals to modify gene expression in cardiac tissue
US20070027490A1 (en) * 1996-09-16 2007-02-01 Shlomo Ben-Haim Fencing of Cardiac Muscles
US7203535B1 (en) 1999-04-01 2007-04-10 Cardiac Pacemakers, Inc. System and method for classifying tachycardia arrhythmias having 1:1 atrial-to-ventricular rhythms
US20070096897A1 (en) * 2005-10-31 2007-05-03 Welch Allyn, Inc. Attachment/location monitoring of a signal generating entity
US20070129641A1 (en) * 2005-12-01 2007-06-07 Sweeney Robert J Posture estimation at transitions between states
US20070150010A1 (en) * 2005-12-22 2007-06-28 Scott Stubbs Cardiac pacemaker with pacing rate monitoring
US20070171211A1 (en) * 2003-02-10 2007-07-26 N-Trig Ltd. Touch detection for a digitizer
US20070233201A1 (en) * 2000-05-26 2007-10-04 Cardiac Pacemakers, Inc. Rate smoothing control
US20070255323A1 (en) * 2006-04-28 2007-11-01 Medtronic, Inc. Implantable medical device for the concurrent treatment of a plurality of neurological disorders and method therefore
US20070293901A1 (en) * 2004-03-10 2007-12-20 Impulse Dynamics Nv Protein activity modification
US20080037033A1 (en) * 2004-06-14 2008-02-14 Isra Vision Systems Ag Sensor For Measuring The Surface Of An Object
US7460907B1 (en) 1998-07-20 2008-12-02 Impulse Dynamics N.V. Pacing with hemodynamic enhancement
US20090062893A1 (en) * 2005-03-18 2009-03-05 Meta Cure Limited Pancreas lead
US20090088816A1 (en) * 1999-03-05 2009-04-02 Tami Harel Gastrointestinal Methods And Apparatus For Use In Treating Disorders And Controlling Blood Sugar
US20090149907A1 (en) * 2007-12-11 2009-06-11 Cardiac Pacemakers, Inc. Av delay features
EP2075014A2 (en) 2002-05-24 2009-07-01 Angiotech International Ag Compositions and methods for coating medical implants
US20100016923A1 (en) * 2004-03-10 2010-01-21 Impulse Dynamics Nv Protein activity modification
US7668590B1 (en) 2004-04-20 2010-02-23 Pacesetter, Inc. Methods and devices for determining exercise diagnostic parameters
US7676262B1 (en) 2004-04-20 2010-03-09 Pacesetter, Inc. Methods and devices for determining exercise compliance diagnostics
US20100121402A1 (en) * 2008-11-10 2010-05-13 Shantha Arcot-Krishnamurthy Reverse hysteresis and mode switching for intermittent pacing therapy
US7840264B1 (en) 1996-08-19 2010-11-23 Mr3 Medical, Llc System and method for breaking reentry circuits by cooling cardiac tissue
US20110009641A1 (en) * 2005-06-15 2011-01-13 Anderson Daniel G Amine-containing lipids and uses thereof
US7908003B1 (en) 1996-08-19 2011-03-15 Mr3 Medical Llc System and method for treating ischemia by improving cardiac efficiency
US7953481B1 (en) 1999-10-25 2011-05-31 Impulse Dynamics N.V. Anti-arrhythmic device and a method of delivering anti-arrhythmic cardiac therapy
US20110144526A1 (en) * 2005-05-11 2011-06-16 Stahmann Jeffrey E Enhancements to the detection of pulmonary edema when using transthoracic impedance
WO2012126503A1 (en) 2011-03-18 2012-09-27 St. Jude Medical Ab Hemodynamic status assessment
US8321013B2 (en) 1996-01-08 2012-11-27 Impulse Dynamics, N.V. Electrical muscle controller and pacing with hemodynamic enhancement
US8478407B2 (en) * 2011-07-28 2013-07-02 Medtronic, Inc. Methods for promoting intrinsic activation in single chamber implantable cardiac pacing systems
US8934975B2 (en) 2010-02-01 2015-01-13 Metacure Limited Gastrointestinal electrical therapy
US8969353B2 (en) 2008-11-07 2015-03-03 Massachusetts Institute Of Technology Aminoalcohol lipidoids and uses thereof
US9066662B2 (en) 2007-04-04 2015-06-30 Pacesetter, Inc. System and method for estimating cardiac pressure based on cardiac electrical conduction delays using an implantable medical device
US9101765B2 (en) 1999-03-05 2015-08-11 Metacure Limited Non-immediate effects of therapy
US9113789B2 (en) 2007-04-04 2015-08-25 Pacesetter, Inc. System and method for estimating electrical conduction delays from immittance values measured using an implantable medical device
US9181321B2 (en) 2013-03-14 2015-11-10 Shire Human Genetic Therapies, Inc. CFTR mRNA compositions and related methods and uses
US9193827B2 (en) 2010-08-26 2015-11-24 Massachusetts Institute Of Technology Poly(beta-amino alcohols), their preparation, and uses thereof
US9238716B2 (en) 2011-03-28 2016-01-19 Massachusetts Institute Of Technology Conjugated lipomers and uses thereof
US9289618B1 (en) 1996-01-08 2016-03-22 Impulse Dynamics Nv Electrical muscle controller
US9308281B2 (en) 2011-06-08 2016-04-12 Shire Human Genetic Therapies, Inc. MRNA therapy for Fabry disease
US9315472B2 (en) 2013-05-01 2016-04-19 Massachusetts Institute Of Technology 1,3,5-triazinane-2,4,6-trione derivatives and uses thereof
US9320448B2 (en) 2008-04-18 2016-04-26 Pacesetter, Inc. Systems and methods for improved atrial fibrillation (AF) monitoring
US9522176B2 (en) 2013-10-22 2016-12-20 Shire Human Genetic Therapies, Inc. MRNA therapy for phenylketonuria
US9629804B2 (en) 2013-10-22 2017-04-25 Shire Human Genetic Therapies, Inc. Lipid formulations for delivery of messenger RNA
US9713723B2 (en) 1996-01-11 2017-07-25 Impulse Dynamics Nv Signal delivery through the right ventricular septum
US9821158B2 (en) 2005-02-17 2017-11-21 Metacure Limited Non-immediate effects of therapy
US9840479B2 (en) 2014-07-02 2017-12-12 Massachusetts Institute Of Technology Polyamine-fatty acid derived lipidoids and uses thereof
US9850269B2 (en) 2014-04-25 2017-12-26 Translate Bio, Inc. Methods for purification of messenger RNA
US9931503B2 (en) 2003-03-10 2018-04-03 Impulse Dynamics Nv Protein activity modification
US9957499B2 (en) 2013-03-14 2018-05-01 Translate Bio, Inc. Methods for purification of messenger RNA
US10022455B2 (en) 2014-05-30 2018-07-17 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
US10138213B2 (en) 2014-06-24 2018-11-27 Translate Bio, Inc. Stereochemically enriched compositions for delivery of nucleic acids
US10350419B2 (en) 2007-12-13 2019-07-16 Cardiac Pacemakers, Inc. Supraventricular tachy sensing vector
US10576166B2 (en) 2009-12-01 2020-03-03 Translate Bio, Inc. Liver specific delivery of messenger RNA
US10864378B2 (en) 2017-03-09 2020-12-15 Cardiac Pacemakers, Inc. Pacemaker with diagnostic intrinsic beat search
US11174500B2 (en) 2018-08-24 2021-11-16 Translate Bio, Inc. Methods for purification of messenger RNA
US11173190B2 (en) 2017-05-16 2021-11-16 Translate Bio, Inc. Treatment of cystic fibrosis by delivery of codon-optimized mRNA encoding CFTR
US11224642B2 (en) 2013-10-22 2022-01-18 Translate Bio, Inc. MRNA therapy for argininosuccinate synthetase deficiency
US11253605B2 (en) 2017-02-27 2022-02-22 Translate Bio, Inc. Codon-optimized CFTR MRNA
US11254936B2 (en) 2012-06-08 2022-02-22 Translate Bio, Inc. Nuclease resistant polynucleotides and uses thereof
US11439815B2 (en) 2003-03-10 2022-09-13 Impulse Dynamics Nv Protein activity modification
US11779768B2 (en) 2004-03-10 2023-10-10 Impulse Dynamics Nv Protein activity modification
US11951180B2 (en) 2023-04-03 2024-04-09 Translate Bio, Inc. Lipid nanoparticle compositions and methods for MRNA delivery

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5522859A (en) * 1993-09-29 1996-06-04 Medtronic, Inc. Sinus preference method and apparatus for cardiac pacemakers
FR2734730B1 (en) * 1995-05-31 1997-08-22 Ela Medical Sa ACTIVE IMPLANTABLE MEDICAL DEVICE, IN PARTICULAR A CARDIAC STIMULATOR OR DEFRIBRILLATOR
SE9603635D0 (en) 1996-10-04 1996-10-04 Pacesetter Ab Implantable stimulator
US7319900B2 (en) 2003-12-11 2008-01-15 Cardiac Pacemakers, Inc. Cardiac response classification using multiple classification windows
US8521284B2 (en) 2003-12-12 2013-08-27 Cardiac Pacemakers, Inc. Cardiac response classification using multisite sensing and pacing
US7761162B2 (en) * 2004-12-13 2010-07-20 Cardiac Pacemakers, Inc. Capture verification with intrinsic response discrimination
US7392088B2 (en) * 2005-04-28 2008-06-24 Cardiac Pacemakers, Inc. Capture detection for multi-chamber pacing
US7529578B2 (en) * 2005-07-12 2009-05-05 Cardiac Pacemakers, Inc. Multi channel approach to capture verification

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3661157A (en) * 1969-04-16 1972-05-09 Nat Res Dev Inhibited demand pacer with a two-rate pulse generator
US3857399A (en) * 1970-03-24 1974-12-31 F Zacouto Heart pacer
US3921642A (en) * 1974-07-01 1975-11-25 Thomas A Preston Automatic rate adjustment pacer with natural rate searching means and method of operation
US4169480A (en) * 1977-08-19 1979-10-02 Biotronik Mess- Und Therapiegerate Gmbh & Co. Demand pacer with programmable rate hysteresis
US4363325A (en) * 1981-01-19 1982-12-14 Medtronic, Inc. Mode adaptive pacer
US4856523A (en) * 1987-10-08 1989-08-15 Siemens-Pacesetter, Inc. Rate-responsive pacemaker with automatic mode switching and/or variable hysteresis rate
US4972834A (en) * 1988-09-30 1990-11-27 Vitatron Medical B.V. Pacemaker with improved dynamic rate responsiveness

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4313442A (en) * 1980-07-21 1982-02-02 Cardiac Pacemakers, Inc. Atrial rate sensitive cardiac pacer apparatus
DE3885876T3 (en) * 1988-02-01 2004-07-15 St. Jude Medical Ab Pacemaker with a hysteresis function.

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3661157A (en) * 1969-04-16 1972-05-09 Nat Res Dev Inhibited demand pacer with a two-rate pulse generator
US3857399A (en) * 1970-03-24 1974-12-31 F Zacouto Heart pacer
US3921642A (en) * 1974-07-01 1975-11-25 Thomas A Preston Automatic rate adjustment pacer with natural rate searching means and method of operation
US4169480A (en) * 1977-08-19 1979-10-02 Biotronik Mess- Und Therapiegerate Gmbh & Co. Demand pacer with programmable rate hysteresis
US4363325A (en) * 1981-01-19 1982-12-14 Medtronic, Inc. Mode adaptive pacer
US4856523A (en) * 1987-10-08 1989-08-15 Siemens-Pacesetter, Inc. Rate-responsive pacemaker with automatic mode switching and/or variable hysteresis rate
US4972834A (en) * 1988-09-30 1990-11-27 Vitatron Medical B.V. Pacemaker with improved dynamic rate responsiveness

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
"Dual Chamber Pacing Aborts Vasovagal Syncope Induced by Head-Up 60° Tilt", Fitzpatrick et al. PACE, vol. 14, pp. 13-19.
Dual Chamber Pacing Aborts Vasovagal Syncope Induced by Head Up 60 Tilt , Fitzpatrick et al. PACE, vol. 14, pp. 13 19. *

Cited By (266)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5501701A (en) * 1994-04-29 1996-03-26 Medtronic, Inc. Pacemaker with vasovagal syncope detection and therapy
EP1374947A2 (en) 1994-04-29 2004-01-02 Medtronic, Inc. Pacemaker with vasovagal syncope detection
US5540728A (en) * 1994-05-20 1996-07-30 Medtronic, Inc. Pacemaker with vasovagal snycope detection
US5676686A (en) * 1994-05-20 1997-10-14 Medtronic, Inc. Pacemaker with vasovagal syncope detection
US5725561A (en) * 1995-06-09 1998-03-10 Medtronic, Inc. Method and apparatus for variable rate cardiac stimulation
US5814083A (en) * 1995-09-29 1998-09-29 Medtronic, Inc Pacemaker tachy determination based blocked on 2:1 sensing
WO1997011745A1 (en) * 1995-09-29 1997-04-03 Medtronic, Inc. Modification of pacemaker tachy response based on ffrw sensing
EP1334746A1 (en) 1995-09-29 2003-08-13 Medtronic, Inc. Pacemaker tachy determination based on blocked 2:1 sensing
EP1275413A1 (en) 1995-09-29 2003-01-15 Medtronic, Inc. Pacemaker tachy determination based on blocked 2:1 sensing
US5759196A (en) * 1995-09-29 1998-06-02 Medtronic, Inc. Modification of pacemaker tachy response based on FFRW sensing
US9289618B1 (en) 1996-01-08 2016-03-22 Impulse Dynamics Nv Electrical muscle controller
US20070088393A1 (en) * 1996-01-08 2007-04-19 Shlomo Ben-Haim Electrical Muscle Controller
US7062318B2 (en) 1996-01-08 2006-06-13 Impulse Dynamics (Israel) Ltd Electrical muscle controller
US20040243190A1 (en) * 1996-01-08 2004-12-02 Shlomo Ben-Haim Electrical muscle controller
US8825152B2 (en) 1996-01-08 2014-09-02 Impulse Dynamics, N.V. Modulation of intracellular calcium concentration using non-excitatory electrical signals applied to the tissue
US7167748B2 (en) 1996-01-08 2007-01-23 Impulse Dynamics Nv Electrical muscle controller
US8321013B2 (en) 1996-01-08 2012-11-27 Impulse Dynamics, N.V. Electrical muscle controller and pacing with hemodynamic enhancement
US8260416B2 (en) 1996-01-08 2012-09-04 Impulse Dynamics, N.V. Electrical muscle controller
US8311629B2 (en) 1996-01-08 2012-11-13 Impulse Dynamics, N.V. Electrical muscle controller
US20080058879A1 (en) * 1996-01-08 2008-03-06 Shlomo Ben-Haim Electrical Muscle Controller
US8306616B2 (en) 1996-01-08 2012-11-06 Impulse Dynamics, N.V. Electrical muscle controller
US20070239216A9 (en) * 1996-01-08 2007-10-11 Itzik Shemer Modulation of intracellular calcium concentration using non-excitatory electrical signals applied to the tissue
US8301247B2 (en) 1996-01-08 2012-10-30 Impulse Dynamics, N.V. Electrical muscle controller
US20030040777A1 (en) * 1996-01-08 2003-02-27 Itzik Shemer Modulation of intracellular calcium concentration using non-excitatory electrical signals applied to the tissue
US8306617B2 (en) 1996-01-08 2012-11-06 Impulse Dynamics N.V. Electrical muscle controller
US20020052632A1 (en) * 1996-01-08 2002-05-02 Shlomo Ben-Haim Electrical muscle controller
US9713723B2 (en) 1996-01-11 2017-07-25 Impulse Dynamics Nv Signal delivery through the right ventricular septum
US5713929A (en) * 1996-05-03 1998-02-03 Medtronic, Inc. Arrhythmia and fibrillation prevention pacemaker using ratchet up and decay modes of operation
DE19623046A1 (en) * 1996-05-28 1997-12-04 Biotronik Mess & Therapieg Pacemaker with hysteresis function
WO1997045161A1 (en) * 1996-05-28 1997-12-04 Biotronik Mess-und Therapiegeräte GmbH & Co. Ingenieurbüro Berlin Demand pacemaker with hysteresis function
US5706829A (en) * 1996-06-06 1998-01-13 Creighton University Method for treating neurocardiogenic syncope
US7908003B1 (en) 1996-08-19 2011-03-15 Mr3 Medical Llc System and method for treating ischemia by improving cardiac efficiency
US7840264B1 (en) 1996-08-19 2010-11-23 Mr3 Medical, Llc System and method for breaking reentry circuits by cooling cardiac tissue
US20070027490A1 (en) * 1996-09-16 2007-02-01 Shlomo Ben-Haim Fencing of Cardiac Muscles
US5782886A (en) * 1997-02-28 1998-07-21 Vitatron Medical, B.V. Pacemaker with improved hysteresis
EP0861677A2 (en) 1997-02-28 1998-09-02 Vitatron Medical B.V. Pacemaker with improved hysteresis
EP0861677A3 (en) * 1997-02-28 1999-06-09 Vitatron Medical B.V. Pacemaker with improved hysteresis
US6078836A (en) * 1997-05-16 2000-06-20 Ela Medical S.A. Active implantable medical device for the reduction of cardiac arrhythmias by modifying the escape interval and methods therefor
FR2763247A1 (en) * 1997-05-16 1998-11-20 Ela Medical Sa ACTIVE IMPLANTABLE MEDICAL DEVICE, IN PARTICULAR A CARDIAC STIMULATOR, DEFIBRILLATOR AND / OR CARDIOVERTER FOR REDUCING ARRHYTHMIA EPISODES, ESPECIALLY ATRIAL ARRHYTHMIA
EP0880979A1 (en) * 1997-05-16 1998-12-02 ELA MEDICAL (Société anonyme) Atrial arrhythmia reducing pacemaker, defibrillator and/or cardioverter
US7460907B1 (en) 1998-07-20 2008-12-02 Impulse Dynamics N.V. Pacing with hemodynamic enhancement
EP0990452A2 (en) 1998-09-30 2000-04-05 Vitatron Medical B.V. Pacing system with full range sudden rate drop detection and responsive pacing intervention
US5991659A (en) * 1998-09-30 1999-11-23 Vitatron Medical, B.V. Pacing system with full range sudden rate drop detection and responsive pacing intervention
US20040215267A1 (en) * 1998-11-06 2004-10-28 Shlomo Ben-Haim Regulation of excitable tissue control of the heart based on physiological input
WO2000027475A1 (en) * 1998-11-06 2000-05-18 Impulse Dynamics Nv Sensor-based regulation of excitable tissue control of the heart
US6675043B1 (en) 1998-11-06 2004-01-06 Impulse Dynamics N.V. Sensor-based regulation of excitable tissue control of the heart
US7310555B2 (en) 1998-11-06 2007-12-18 Impulse Dynamics N.V. Regulation of excitable tissue control of the heart based on physiological input
US6725093B1 (en) 1998-11-06 2004-04-20 Impulse Dynamics N.V. Regulation of excitable tissue control of the heart based on physiological input
US6587721B1 (en) 1998-11-06 2003-07-01 Impulse Dynamics N.V. Trigger-based regulation of excitable tissue control of the heart
US7678573B2 (en) 1999-02-04 2010-03-16 Pluristem Ltd. Method of preparing a conditioned medium from a confluent stromal cell culture
US20050180958A1 (en) * 1999-02-04 2005-08-18 Technion Research & Development Foundation Ltd. Method and apparatus for maintenance and expansion of hemopoietic stem cells and/or progenitor cells
US20050181504A1 (en) * 1999-02-04 2005-08-18 Technion Research & Development Method and apparatus for maintenance and expansion of hemopoietic stem cells and/or progenitor cells
WO2000051678A1 (en) * 1999-03-01 2000-09-08 Cardiac Pacemakers, Inc. Cardiac rhythm management device with detection and therapy for sudden syncopal events
US6049735A (en) * 1999-03-01 2000-04-11 Cardiac Pacemakers Inc. Cardiac rhythm management device with detection and therapy for sudden syncopal events
US9101765B2 (en) 1999-03-05 2015-08-11 Metacure Limited Non-immediate effects of therapy
US20030055464A1 (en) * 1999-03-05 2003-03-20 Nissim Darvish Blood glucose level control
US8346363B2 (en) 1999-03-05 2013-01-01 Metacure Limited Blood glucose level control
US8019421B2 (en) 1999-03-05 2011-09-13 Metacure Limited Blood glucose level control
US20090088816A1 (en) * 1999-03-05 2009-04-02 Tami Harel Gastrointestinal Methods And Apparatus For Use In Treating Disorders And Controlling Blood Sugar
US20060085045A1 (en) * 1999-03-05 2006-04-20 Metacure N.V. Blood glucose level control
US20060184207A1 (en) * 1999-03-05 2006-08-17 Metacure N.V. Blood glucose level control
US8700161B2 (en) 1999-03-05 2014-04-15 Metacure Limited Blood glucose level control
US8666495B2 (en) 1999-03-05 2014-03-04 Metacure Limited Gastrointestinal methods and apparatus for use in treating disorders and controlling blood sugar
US7203535B1 (en) 1999-04-01 2007-04-10 Cardiac Pacemakers, Inc. System and method for classifying tachycardia arrhythmias having 1:1 atrial-to-ventricular rhythms
US20070135853A1 (en) * 1999-05-21 2007-06-14 Cardiac Pacemakers, Inc. Apparatus and method for ventricular rate regularization
US7856267B2 (en) 1999-05-21 2010-12-21 Cardiac Pacemakers, Inc. Apparatus and method for pacing mode switching during atrial tachyarrhythmias
US6430438B1 (en) 1999-05-21 2002-08-06 Cardiac Pacemakers, Inc. Cardiac rhythm management system with atrial shock timing optimization
US8249703B2 (en) 1999-05-21 2012-08-21 Cardiac Pacemakers, Inc. Apparatus and method for ventricular rate regularization
US20070288062A1 (en) * 1999-05-21 2007-12-13 Cardiac Pacemakers, Inc. Apparatus and method for pacing mode switching during atrial tachyarrhythmias
US6285907B1 (en) 1999-05-21 2001-09-04 Cardiac Pacemakers, Inc. System providing ventricular pacing and biventricular coordination
US6988002B2 (en) 1999-05-21 2006-01-17 Cardiac Pacemakers, Inc. Apparatus and method for ventricular rate regularization with biventricular sensing
US8391974B2 (en) 1999-05-21 2013-03-05 Cardiac Pacemakers, Inc. Apparatus and method for pacing mode switching during atrial tachyarrhythmias
US8135465B2 (en) 1999-05-21 2012-03-13 Cardiac Pacemakers, Inc. System providing ventricular pacing and biventricular coordination
US6351669B1 (en) 1999-05-21 2002-02-26 Cardiac Pacemakers, Inc. Cardiac rhythm management system promoting atrial pacing
US7212860B2 (en) 1999-05-21 2007-05-01 Cardiac Pacemakers, Inc. Apparatus and method for pacing mode switching during atrial tachyarrhythmias
US20090076563A1 (en) * 1999-05-21 2009-03-19 Cardiac Pacemakers, Inc. Method and apparatus for treating irregular ventricular contractions such as during atrial arrhythmia
US7062325B1 (en) 1999-05-21 2006-06-13 Cardiac Pacemakers Inc Method and apparatus for treating irregular ventricular contractions such as during atrial arrhythmia
US6353759B1 (en) 1999-05-21 2002-03-05 Cardiac Pacemakers, Inc. Cardiac rhythm management system promoting a trial pacing
US8064997B2 (en) 1999-05-21 2011-11-22 Cardiac Pacemakers, Inc. Method and apparatus for treating irregular ventricular contractions such as during atrial arrhythmia
US20110087303A1 (en) * 1999-05-21 2011-04-14 Stahmann Jeffrey E Apparatus and method for pacing mode switching during atrial tachyarrhythmias
US20040215259A1 (en) * 1999-05-21 2004-10-28 Cardiac Pacemakers, Inc. Method and apparatus for treating irregular ventricular contractions such as during atrial arrhythmia
US20030233131A1 (en) * 1999-05-21 2003-12-18 Kramer Andrew P. Apparatus and method for ventricular rate regularization
US7120490B2 (en) 1999-05-21 2006-10-10 Cardiac Pacemakers, Inc. Cardiac rhythm management system with atrial shock timing optimization
US7181278B2 (en) 1999-05-21 2007-02-20 Cardiac Pacemakers, Inc. Apparatus and method for ventricular rate regularization
US7460908B2 (en) 1999-05-21 2008-12-02 Cardiac Pacemakers, Inc. System providing ventricular pacing and biventricular coordination
US20070016258A1 (en) * 1999-05-21 2007-01-18 Cardiac Pacemakers, Inc. Method and apparatus for treating irregular ventricular contractions such as during atrial arrhythmia
US20040172076A1 (en) * 1999-05-21 2004-09-02 Stahmann Jeffrey E. Apparatus and method for pacing mode switching during atrial tachyarrhythmias
US6411848B2 (en) 1999-05-21 2002-06-25 Cardiac Pacemakers, Inc. System providing ventricular pacing and biventricular coordination
US7647102B2 (en) 1999-10-25 2010-01-12 Impulse Dynamics N.V. Cardiac contractility modulation device having anti-arrhythmic capabilities and method of operating thereof
US7027863B1 (en) 1999-10-25 2006-04-11 Impulse Dynamics N.V. Device for cardiac therapy
US7953481B1 (en) 1999-10-25 2011-05-31 Impulse Dynamics N.V. Anti-arrhythmic device and a method of delivering anti-arrhythmic cardiac therapy
US20060212079A1 (en) * 1999-10-25 2006-09-21 Routh Andre G Cardiac contractility modulation device having anti-arrhythmic capabilities and method of operating thereof
US20020091415A1 (en) * 2000-05-13 2002-07-11 Lovett Eric G. Rate smoothing control
US7039461B1 (en) 2000-05-13 2006-05-02 Cardiac Pacemakers, Inc. Cardiac pacing system for prevention of ventricular fibrillation and ventricular tachycardia episode
US8239021B2 (en) 2000-05-13 2012-08-07 Cardiac Pacemakers, Inc. Cardiac pacing system for prevention of ventricular fibrillation and ventricular tachycardia episode
US20100249866A1 (en) * 2000-05-13 2010-09-30 Lovett Eric G Cardiac pacing system for prevention of ventricular fibrillation and ventricular tachycardia episode
US7239914B2 (en) 2000-05-13 2007-07-03 Cardiac Pacemakers, Inc. Rate smoothing control
US7742814B2 (en) 2000-05-13 2010-06-22 Cardiac Pacemakers, Inc. Cardiac pacing system for prevention of ventricular fibrillation and ventricular tachycardia episode
US6647295B2 (en) 2000-05-15 2003-11-11 Pacesetter, Inc. Implantable cardiac stimulation device with detection and therapy for patients with vasovagal syncope
US6625492B2 (en) 2000-05-15 2003-09-23 Pacesetter, Inc. Implantable cardiac stimulation device with detection and therapy for patients with vasovagal syncope
US20030078630A1 (en) * 2000-05-26 2003-04-24 Cardiac Pacemakers, Inc. Rate smoothing control
US7069077B2 (en) 2000-05-26 2006-06-27 Cardiac Pacemakers, Inc. Rate smoothing control
US20070233201A1 (en) * 2000-05-26 2007-10-04 Cardiac Pacemakers, Inc. Rate smoothing control
US8512220B2 (en) 2000-05-26 2013-08-20 Cardiac Pacemakers, Inc. Rate smoothing control
US6522922B1 (en) 2000-07-13 2003-02-18 Cardiac Pacemakers, Inc. Method and apparatus for breaking pacemaker mediated bradycardia
US20050038480A1 (en) * 2000-07-13 2005-02-17 Cardiac Pacemakers, Inc. Ventricular conduction delay trending system and method
US7383086B2 (en) 2000-07-13 2008-06-03 Cardiac Pacemakers, Inc. Ventricular conduction delay trending system and method
US7403817B2 (en) 2000-07-13 2008-07-22 Cardiac Pacemakers, Inc. Method and apparatus for breaking pacemaker mediated bradycardia
US6763267B2 (en) 2000-07-13 2004-07-13 Cardiac Pacemakers, Inc. Ventricular conduction delay trending system and method
US20040249421A1 (en) * 2000-09-13 2004-12-09 Impulse Dynamics Nv Blood glucose level control
US8046061B2 (en) 2000-09-14 2011-10-25 Cardiac Pacemakers, Inc. System and method for preventing recurrence of atrial tachyarrhythmia
US20050060000A1 (en) * 2000-09-14 2005-03-17 Cardiac Pacemakers, Inc. System and method for preventing recurrence of atrial tachyarrhythmia
US6829504B1 (en) 2000-09-14 2004-12-07 Cardiac Pacemakers, Inc. System and method for preventing recurrence of atrial tachyarrhythmia
US7421294B2 (en) 2000-09-14 2008-09-02 Cardiac Pacemakers, Inc. System and method for preventing recurrence of atrial tachyarrhythmia
US6687541B2 (en) 2000-09-14 2004-02-03 Cardiac Pacemakers, Inc. Method for delivering atrial defibrillation therapy
US20080319494A1 (en) * 2000-09-14 2008-12-25 Cardiac Pacemakers, Inc. System and method for preventing recurrence of atrial tachyarrhythmia
WO2002045792A2 (en) 2000-12-04 2002-06-13 Medtronic, Inc. Method and system for preventing the recurrence of atrial fibrillation by an implantable medical device
US20070073348A1 (en) * 2000-12-26 2007-03-29 Cardiac Pacemakers, Inc. Apparatus and method for pacing mode switching during atrial tachyarrhythmias
US8103334B2 (en) 2000-12-26 2012-01-24 Cardiac Pacemakers, Inc. Method and system for display of cardiac event intervals in a resynchronization pacemaker
US20020082660A1 (en) * 2000-12-26 2002-06-27 Stahmann Jeffrey E Apparatus and method for pacing mode switching during atrial tachyarrhythmias
US6501988B2 (en) 2000-12-26 2002-12-31 Cardiac Pacemakers Inc. Apparatus and method for ventricular rate regularization with biventricular sensing
US7805192B2 (en) 2000-12-26 2010-09-28 Cardiac Pacemakers, Inc. Apparatus and method for pacing mode switching during atrial tachyarrhythmias
US7142918B2 (en) 2000-12-26 2006-11-28 Cardiac Pacemakers, Inc. Apparatus and method for pacing mode switching during atrial tachyarrhythmias
US20040243188A1 (en) * 2000-12-26 2004-12-02 Cardiac Pacemakers, Inc. Method and system for display of cardiac event intervals in a resynchronization pacemaker
US20020082509A1 (en) * 2000-12-26 2002-06-27 Scott Vanderlinde Method and system for display of cardiac event intervals in a resynchronization pacemaker
US7047066B2 (en) 2000-12-26 2006-05-16 Cardiac Pacemakers, Inc. Method and system for display of cardiac event intervals in a resynchronization pacemaker
US7680530B2 (en) 2000-12-26 2010-03-16 Cardiac Pacemakers, Inc. Method and system for display of cardiac event intervals in a resynchronization pacemaker
US20100145407A1 (en) * 2000-12-26 2010-06-10 Scott Vanderlinde Method and system for display of cardiac event intervals in a resynchronization pacemaker
US6957100B2 (en) 2000-12-26 2005-10-18 Cardiac Pacemakers, Inc. Method and system for display of cardiac event intervals in a resynchronization pacemaker
US20040010295A1 (en) * 2000-12-29 2004-01-15 Cardiac Pacemakers, Inc. Apparatus and method for ventricular rate regularization
US7142915B2 (en) 2000-12-29 2006-11-28 Cardiac Pacemakers, Inc. Apparatus and method for ventricular rate regularization
US6889078B2 (en) 2001-04-26 2005-05-03 Medtronic, Inc. Hysteresis activation of accelerated pacing
US6895275B2 (en) 2002-01-22 2005-05-17 Medtronic, Inc. Methods and apparatus for detection and treatment of syncope
WO2003061759A1 (en) 2002-01-22 2003-07-31 Medtronic, Inc. Methods and apparatus for detection and treatment of syncope
EP2075014A2 (en) 2002-05-24 2009-07-01 Angiotech International Ag Compositions and methods for coating medical implants
US8676336B2 (en) 2002-10-11 2014-03-18 Cardiac Pacemaker, Inc. Methods and devices for detection of context when addressing a medical condition of a patient
US7986998B2 (en) 2002-10-11 2011-07-26 Cardiac Pacemakers, Inc. Methods and devices for detection of context when addressing a medical condition of a patient
US20040073093A1 (en) * 2002-10-11 2004-04-15 Cardiac Pacemakers, Inc. Methods and devices for detection of context when addressing a medical condition of a patient
US7400928B2 (en) 2002-10-11 2008-07-15 Cardiac Pacemakers, Inc. Methods and devices for detection of context when addressing a medical condition of a patient
US8228311B2 (en) 2003-02-10 2012-07-24 N-Trig Ltd. Touch detection for a digitizer
US20070171211A1 (en) * 2003-02-10 2007-07-26 N-Trig Ltd. Touch detection for a digitizer
US7843439B2 (en) 2003-02-10 2010-11-30 N-Trig Ltd. Touch detection for a digitizer
US20070027487A1 (en) * 2003-03-10 2007-02-01 Impulse Dynamics Nv Apparatus and method for delivering electrical signals to modify gene expression in cardiac tissue
US8326416B2 (en) 2003-03-10 2012-12-04 Impulse Dynamics Nv Apparatus and method for delivering electrical signals to modify gene expression in cardiac tissue
US11439815B2 (en) 2003-03-10 2022-09-13 Impulse Dynamics Nv Protein activity modification
US20110093028A1 (en) * 2003-03-10 2011-04-21 Impulse Dynamics Nv Apparatus and method for delivering electrical signals to modify gene expression in cardiac tissue
US7840262B2 (en) 2003-03-10 2010-11-23 Impulse Dynamics Nv Apparatus and method for delivering electrical signals to modify gene expression in cardiac tissue
US9931503B2 (en) 2003-03-10 2018-04-03 Impulse Dynamics Nv Protein activity modification
US7027865B2 (en) 2003-04-16 2006-04-11 Medtronic, Inc. Pacemaker with vasovagal syncope detection and therapy
WO2004093985A1 (en) * 2003-04-16 2004-11-04 Medtronic, Inc. Pacemaker with vasovagal syncope detection and therapy
US20040210260A1 (en) * 2003-04-16 2004-10-21 Medtronic, Inc. Pacemaker with vasovagal syncope detection and therapy
US8792985B2 (en) 2003-07-21 2014-07-29 Metacure Limited Gastrointestinal methods and apparatus for use in treating disorders and controlling blood sugar
US20070027493A1 (en) * 2003-07-21 2007-02-01 Shlomo Ben-Haim Gastrointestinal methods and apparatus for use in treating disorders and controlling blood sugar
WO2005034745A1 (en) * 2003-10-10 2005-04-21 Medtronic, Inc. Method and apparatus for detecting and discriminating arrhythmias
US20050080347A1 (en) * 2003-10-10 2005-04-14 Medtronic, Inc. Method and apparatus for detecting and discriminating arrhythmias
US7076290B2 (en) 2003-10-10 2006-07-11 Medtronic, Inc. Method and apparatus for detecting and discriminating arrhythmias
US20050137633A1 (en) * 2003-12-22 2005-06-23 Salo Rodney W. Pacing method and device for preserving native conduction system
US7194307B2 (en) 2003-12-22 2007-03-20 Cardiac Pacemakers, Inc. Pacing method and device for preserving native conduction system
US8548583B2 (en) 2004-03-10 2013-10-01 Impulse Dynamics Nv Protein activity modification
US20070293901A1 (en) * 2004-03-10 2007-12-20 Impulse Dynamics Nv Protein activity modification
US8352031B2 (en) 2004-03-10 2013-01-08 Impulse Dynamics Nv Protein activity modification
US10352948B2 (en) 2004-03-10 2019-07-16 Impulse Dynamics Nv Protein activity modification
US20100016923A1 (en) * 2004-03-10 2010-01-21 Impulse Dynamics Nv Protein activity modification
US11779768B2 (en) 2004-03-10 2023-10-10 Impulse Dynamics Nv Protein activity modification
US7676262B1 (en) 2004-04-20 2010-03-09 Pacesetter, Inc. Methods and devices for determining exercise compliance diagnostics
US7668590B1 (en) 2004-04-20 2010-02-23 Pacesetter, Inc. Methods and devices for determining exercise diagnostic parameters
US7822472B1 (en) 2004-04-20 2010-10-26 Pacesetter, Inc. Methods and systems for optimizing exercise compliance diagnostic parameters
US8165667B2 (en) 2004-04-20 2012-04-24 Pacesetter, Inc. Methods and systems for optimizing exercise compliance diagnostic parameters
US20110166463A1 (en) * 2004-04-20 2011-07-07 Cecilia Qin Xi Methods and systems for optimizing exercise compliance diagnostic parameters
US7917197B1 (en) 2004-04-20 2011-03-29 Pacesetter, Inc. Methods and devices for determining exercise diagnostic parameters
US20080037033A1 (en) * 2004-06-14 2008-02-14 Isra Vision Systems Ag Sensor For Measuring The Surface Of An Object
US9821158B2 (en) 2005-02-17 2017-11-21 Metacure Limited Non-immediate effects of therapy
US8244371B2 (en) 2005-03-18 2012-08-14 Metacure Limited Pancreas lead
US20090062893A1 (en) * 2005-03-18 2009-03-05 Meta Cure Limited Pancreas lead
US20110144526A1 (en) * 2005-05-11 2011-06-16 Stahmann Jeffrey E Enhancements to the detection of pulmonary edema when using transthoracic impedance
US8483818B2 (en) 2005-05-11 2013-07-09 Cardiac Pacemakers, Inc. Enhancements to the detection of pulmonary edema when using transthoracic impedance
US20110009641A1 (en) * 2005-06-15 2011-01-13 Anderson Daniel G Amine-containing lipids and uses thereof
US9006487B2 (en) 2005-06-15 2015-04-14 Massachusetts Institute Of Technology Amine-containing lipids and uses thereof
US20070096897A1 (en) * 2005-10-31 2007-05-03 Welch Allyn, Inc. Attachment/location monitoring of a signal generating entity
US20070129641A1 (en) * 2005-12-01 2007-06-07 Sweeney Robert J Posture estimation at transitions between states
US20110046689A1 (en) * 2005-12-22 2011-02-24 Scott Stubbs Cardiac pacemaker with pacing rate monitoring
US8364261B2 (en) 2005-12-22 2013-01-29 Cardiac Pacemakers, Inc. Cardiac pacemaker with pacing rate monitoring
US20070150010A1 (en) * 2005-12-22 2007-06-28 Scott Stubbs Cardiac pacemaker with pacing rate monitoring
US7826897B2 (en) 2005-12-22 2010-11-02 Cardiac Pacemakers, Inc. Cardiac pacemaker with pacing rate monitoring
US8326431B2 (en) 2006-04-28 2012-12-04 Medtronic, Inc. Implantable medical device for the concurrent treatment of a plurality of neurological disorders and method therefore
US20070255323A1 (en) * 2006-04-28 2007-11-01 Medtronic, Inc. Implantable medical device for the concurrent treatment of a plurality of neurological disorders and method therefore
US9113789B2 (en) 2007-04-04 2015-08-25 Pacesetter, Inc. System and method for estimating electrical conduction delays from immittance values measured using an implantable medical device
US9066662B2 (en) 2007-04-04 2015-06-30 Pacesetter, Inc. System and method for estimating cardiac pressure based on cardiac electrical conduction delays using an implantable medical device
US8886308B2 (en) 2007-12-11 2014-11-11 Cardiac Pacemakers, Inc. AV delay features
US20090149907A1 (en) * 2007-12-11 2009-06-11 Cardiac Pacemakers, Inc. Av delay features
US8126551B2 (en) 2007-12-11 2012-02-28 Cardiac Pacemakers, Inc. AV delay features
US11504538B2 (en) 2007-12-13 2022-11-22 Cardiac Pacemakers, Inc. Supraventricular tachy sensing vector
US10350419B2 (en) 2007-12-13 2019-07-16 Cardiac Pacemakers, Inc. Supraventricular tachy sensing vector
US9320448B2 (en) 2008-04-18 2016-04-26 Pacesetter, Inc. Systems and methods for improved atrial fibrillation (AF) monitoring
US10189802B2 (en) 2008-11-07 2019-01-29 Massachusetts Institute Of Technology Aminoalcohol lipidoids and uses thereof
US8969353B2 (en) 2008-11-07 2015-03-03 Massachusetts Institute Of Technology Aminoalcohol lipidoids and uses thereof
US10844028B2 (en) 2008-11-07 2020-11-24 Massachusetts Institute Of Technology Aminoalcohol lipidoids and uses thereof
US11414393B2 (en) 2008-11-07 2022-08-16 Massachusetts Institute Of Technology Aminoalcohol lipidoids and uses thereof
US9556110B2 (en) 2008-11-07 2017-01-31 Massachusetts Institute Of Technology Aminoalcohol lipidoids and uses thereof
US20100121402A1 (en) * 2008-11-10 2010-05-13 Shantha Arcot-Krishnamurthy Reverse hysteresis and mode switching for intermittent pacing therapy
WO2010054359A2 (en) * 2008-11-10 2010-05-14 Cardiac Pacemakers, Inc. Reverse hysteresis and mode switching for intermittent pacing therapy
US8929983B2 (en) 2008-11-10 2015-01-06 Cardiac Pacemakers, Inc. Reverse hysteresis and mode switching for intermittent pacing therapy
WO2010054359A3 (en) * 2008-11-10 2010-10-21 Cardiac Pacemakers, Inc. Reverse hysteresis and mode switching for intermittent pacing therapy
US10576166B2 (en) 2009-12-01 2020-03-03 Translate Bio, Inc. Liver specific delivery of messenger RNA
US8934975B2 (en) 2010-02-01 2015-01-13 Metacure Limited Gastrointestinal electrical therapy
US9193827B2 (en) 2010-08-26 2015-11-24 Massachusetts Institute Of Technology Poly(beta-amino alcohols), their preparation, and uses thereof
WO2012126503A1 (en) 2011-03-18 2012-09-27 St. Jude Medical Ab Hemodynamic status assessment
US10117934B2 (en) 2011-03-28 2018-11-06 Massachusetts Institute Of Technology Conjugated lipomers and uses thereof
US10933139B2 (en) 2011-03-28 2021-03-02 Massachusetts Institute Of Technology Conjugated lipomers and uses thereof
US9238716B2 (en) 2011-03-28 2016-01-19 Massachusetts Institute Of Technology Conjugated lipomers and uses thereof
US11338044B2 (en) 2011-06-08 2022-05-24 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US10350303B1 (en) 2011-06-08 2019-07-16 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US9308281B2 (en) 2011-06-08 2016-04-12 Shire Human Genetic Therapies, Inc. MRNA therapy for Fabry disease
US10888626B2 (en) 2011-06-08 2021-01-12 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US9597413B2 (en) 2011-06-08 2017-03-21 Shire Human Genetic Therapies, Inc. Pulmonary delivery of mRNA
US11730825B2 (en) 2011-06-08 2023-08-22 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US11547764B2 (en) 2011-06-08 2023-01-10 Translate Bio, Inc. Lipid nanoparticle compositions and methods for MRNA delivery
US11291734B2 (en) 2011-06-08 2022-04-05 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US11185595B2 (en) 2011-06-08 2021-11-30 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US11052159B2 (en) 2011-06-08 2021-07-06 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US10238754B2 (en) 2011-06-08 2019-03-26 Translate Bio, Inc. Lipid nanoparticle compositions and methods for MRNA delivery
US10507249B2 (en) 2011-06-08 2019-12-17 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US10413618B2 (en) 2011-06-08 2019-09-17 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US20150005837A1 (en) * 2011-07-28 2015-01-01 Medtronic, Inc. Methods for promoting intrinsic activation in single chamber implantable cardiac pacing systems
US8478407B2 (en) * 2011-07-28 2013-07-02 Medtronic, Inc. Methods for promoting intrinsic activation in single chamber implantable cardiac pacing systems
US9440081B2 (en) * 2011-07-28 2016-09-13 Medtronic, Inc. Methods for promoting intrinsic activation in single chamber implantable cardiac pacing systems
US8755884B2 (en) 2011-07-28 2014-06-17 Medtronic, Inc. Methods for promoting intrinsic activation in single chamber implantable cardiac pacing systems
US9042984B2 (en) * 2011-07-28 2015-05-26 Medtronic, Inc. Methods for promoting intrinsic activation in single chamber implantable cardiac pacing systems
US11254936B2 (en) 2012-06-08 2022-02-22 Translate Bio, Inc. Nuclease resistant polynucleotides and uses thereof
US11510937B2 (en) 2013-03-14 2022-11-29 Translate Bio, Inc. CFTR MRNA compositions and related methods and uses
US11692189B2 (en) 2013-03-14 2023-07-04 Translate Bio, Inc. Methods for purification of messenger RNA
US10420791B2 (en) 2013-03-14 2019-09-24 Translate Bio, Inc. CFTR MRNA compositions and related methods and uses
US9713626B2 (en) 2013-03-14 2017-07-25 Rana Therapeutics, Inc. CFTR mRNA compositions and related methods and uses
US11820977B2 (en) 2013-03-14 2023-11-21 Translate Bio, Inc. Methods for purification of messenger RNA
US10876104B2 (en) 2013-03-14 2020-12-29 Translate Bio, Inc. Methods for purification of messenger RNA
US9181321B2 (en) 2013-03-14 2015-11-10 Shire Human Genetic Therapies, Inc. CFTR mRNA compositions and related methods and uses
US9957499B2 (en) 2013-03-14 2018-05-01 Translate Bio, Inc. Methods for purification of messenger RNA
US9315472B2 (en) 2013-05-01 2016-04-19 Massachusetts Institute Of Technology 1,3,5-triazinane-2,4,6-trione derivatives and uses thereof
US9629804B2 (en) 2013-10-22 2017-04-25 Shire Human Genetic Therapies, Inc. Lipid formulations for delivery of messenger RNA
US11224642B2 (en) 2013-10-22 2022-01-18 Translate Bio, Inc. MRNA therapy for argininosuccinate synthetase deficiency
US11890377B2 (en) 2013-10-22 2024-02-06 Translate Bio, Inc. Lipid formulations for delivery of messenger RNA
US10052284B2 (en) 2013-10-22 2018-08-21 Translate Bio, Inc. Lipid formulations for delivery of messenger RNA
US10493031B2 (en) 2013-10-22 2019-12-03 Translate Bio, Inc. Lipid formulations for delivery of messenger RNA
US10959953B2 (en) 2013-10-22 2021-03-30 Translate Bio, Inc. Lipid formulations for delivery of messenger RNA
US9522176B2 (en) 2013-10-22 2016-12-20 Shire Human Genetic Therapies, Inc. MRNA therapy for phenylketonuria
US9850269B2 (en) 2014-04-25 2017-12-26 Translate Bio, Inc. Methods for purification of messenger RNA
US11059841B2 (en) 2014-04-25 2021-07-13 Translate Bio, Inc. Methods for purification of messenger RNA
US11884692B2 (en) 2014-04-25 2024-01-30 Translate Bio, Inc. Methods for purification of messenger RNA
US10155785B2 (en) 2014-04-25 2018-12-18 Translate Bio, Inc. Methods for purification of messenger RNA
US10293057B2 (en) 2014-05-30 2019-05-21 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
US10912844B2 (en) 2014-05-30 2021-02-09 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
US10286083B2 (en) 2014-05-30 2019-05-14 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
US11433144B2 (en) 2014-05-30 2022-09-06 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
US10022455B2 (en) 2014-05-30 2018-07-17 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
US10286082B2 (en) 2014-05-30 2019-05-14 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
US10493166B2 (en) 2014-05-30 2019-12-03 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
US10138213B2 (en) 2014-06-24 2018-11-27 Translate Bio, Inc. Stereochemically enriched compositions for delivery of nucleic acids
US11104652B2 (en) 2014-06-24 2021-08-31 Translate Bio, Inc. Stereochemically enriched compositions for delivery of nucleic acids
US9840479B2 (en) 2014-07-02 2017-12-12 Massachusetts Institute Of Technology Polyamine-fatty acid derived lipidoids and uses thereof
US11253605B2 (en) 2017-02-27 2022-02-22 Translate Bio, Inc. Codon-optimized CFTR MRNA
US10864378B2 (en) 2017-03-09 2020-12-15 Cardiac Pacemakers, Inc. Pacemaker with diagnostic intrinsic beat search
US11173190B2 (en) 2017-05-16 2021-11-16 Translate Bio, Inc. Treatment of cystic fibrosis by delivery of codon-optimized mRNA encoding CFTR
US11174500B2 (en) 2018-08-24 2021-11-16 Translate Bio, Inc. Methods for purification of messenger RNA
US11951180B2 (en) 2023-04-03 2024-04-09 Translate Bio, Inc. Lipid nanoparticle compositions and methods for MRNA delivery
US11951179B2 (en) 2023-04-03 2024-04-09 Translate Bio, Inc. Lipid nanoparticle compositions and methods for MRNA delivery
US11951181B2 (en) 2023-04-03 2024-04-09 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery

Also Published As

Publication number Publication date
WO1993016756A1 (en) 1993-09-02
USRE37454E1 (en) 2001-11-27
AU3433193A (en) 1993-09-13

Similar Documents

Publication Publication Date Title
US5284491A (en) Cardiac pacemaker with hysteresis behavior
EP0596598B1 (en) Cardiac rhythm management device with automatic optimization of performance related pacing parameters
US5549649A (en) Programmable pacemaker including an atrial rate filter for deriving a filtered atrial rate used for switching pacing modes
US5441523A (en) Forced atrioventricular synchrony dual chamber pacemaker
EP0621055B1 (en) Rate adaptive pacemaker with adjustment of sensor rate as a function of sensed sinus rate
US5318594A (en) DDD type cardiac pacemaker having automatic operating mode switching
EP0796129B1 (en) Cardiac pacemakers using sinus preference method
EP1105188B1 (en) apparatus for prevention of atrial tachyarrhythmias
EP0559847B1 (en) Dual chamber rate responsive pacemaker with automatic mode switching
EP0600631B1 (en) Dual-chamber implantable pacemaker, having adaptive AV interval that prevents ventricular fusion beats
EP0360668B1 (en) Dual chamber rate responsive pacemaker
US7996086B2 (en) Apparatus and method for pacing mode switching during atrial tachyarrhythmias
US5085215A (en) Metabolic demand driven rate-responsive pacemaker
EP0363015B1 (en) Rate stabilization pacemaker
AU653097B2 (en) Dual chamber pacemaker system and method for delivering atrial sync pulses
US8391974B2 (en) Apparatus and method for pacing mode switching during atrial tachyarrhythmias
US5123412A (en) Dual-chamber pacemaker with automatic selection of atrial refractory period
US5968081A (en) System and method for providing improved fallback response in a dual-chamber cardiac pacemaker
EP0559193A2 (en) Implantable pacemaker providing hysteresis in dual-chamber modes
EP1038548B1 (en) Pacemaker
JP4347699B2 (en) Pacemaker with adaptive arrhythmia detection window
EP0148486B1 (en) Improved rate adaptive pacemaker apparatus

Legal Events

Date Code Title Description
AS Assignment

Owner name: MEDTRONIC, INC., MINNESOTA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNORS:SUTTON, RICHARD;BOURGEOIS, IVAN;REEL/FRAME:006089/0504;SIGNING DATES FROM 19911202 TO 19920226

STCF Information on status: patent grant

Free format text: PATENTED CASE

RF Reissue application filed

Effective date: 19951024

FEPP Fee payment procedure

Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

FPAY Fee payment

Year of fee payment: 4

FPAY Fee payment

Year of fee payment: 8